βB2晶体蛋白基因敲除可引起白内障并降低C57BL/C小鼠生殖功能
|
摘要
晶状体中的蛋白质主要包括晶体蛋白(crystallins)、膜蛋白(membraneprotein)和细胞骨架蛋白(cytosteletal protein)等。按水溶性与否可分为可溶性蛋白(晶体蛋白)、非可溶性蛋白(膜蛋白、细胞骨架蛋白、聚合的晶体蛋白)。人晶状体内90%的可溶性蛋白是晶体蛋白:分别是α、β和γ晶体蛋白。
目前对α-晶体蛋白的功能研究比较广泛,它的分子伴侣作用已得到世界公认。对β-晶体蛋白的研究还比较少,其中βB2晶体蛋白(βB2 crystallin,Crybb2)在β族晶体蛋白中含量最高,而且它的水溶性成分呈年龄依赖性增高,因此,它的正常结构及其水溶性成分水平,对维持晶状体的高折射系数和透明至关重要。这种反常性增高势必包含了它在维持晶状体透光性中的重要作用,因此它的功能值得进一步研究。
基因敲除是研究蛋白功能的一个重要手段,已有研究证明α-晶体蛋白基因敲除可以导致白内障,而且α或β-晶体蛋白基因突变也可以导致白内障。文献报道Crybb2基因突变可降低生殖功能。目前国内外尚未有Crybb2基因敲除动物模型的报道,因此我们选择此蛋白作为靶点,利用Crybb2基因敲除小鼠模型,来研究该蛋白在维持晶状体透明性中的作用和其晶状体外生物学功能。
本文主要通过观察Crybb2基因敲除对小鼠晶状体结构的影响及其在晶状体内和晶状体外组织的定位,分析该蛋白在维持晶状体透明性中的作用并研究其晶状体外功能。
主要方法:
1.Crybb2基因敲除小鼠模型的建立及鉴定
此部分工作是应第二军医大学第一附属医院中心实验室要求,与美国纽约iGTL实验室合作并最终在美国iGTL实验室完成,最后以馈赠方式供我们研究专用。小鼠品系为C57BL/C小鼠,小鼠模型为10只杂合子,已成功进行繁殖超过30代,子代小鼠生长发育状况良好。
取鼠尾末端组织,通过PCR技术对小鼠基因型进行鉴定;取小鼠眼晶状体进行匀浆离心后取上清液,通过Western blot技术对晶体蛋白的表达进行鉴定。鉴定后将小鼠分类饲养繁殖。
2.Crybb2基因敲除小鼠晶状体结构特征
用暗视野显微镜观察经氧化损伤后晶状体体外培养的混浊程度。HE染色观察晶状体囊膜下皮质的厚度随年龄的变化,并与野生型同品系小鼠对比。免疫组织化学研究其在晶状体内的定位。
3.Crybb2基因敲除小鼠晶状体外功能研究
图形视网膜电图(pattern electroretinogram,P-ERG)研究Crybb2基因敲除后视觉电生理的改变。Western Blot,PCR和免疫组织化学方法检测Crybb2 mRNA,Crybb2在晶状体外阳性表达(视网膜、大脑、脊髓、睾丸、卵巢),尽管是低水平表达。数小鼠产仔数,精子计数,睾丸称重,大体形态和HE染色观察形态学改变研究Crybb2基因敲除后小鼠生殖功能的改变,并与野生型同品系小鼠对比。
实验结果:
1.Crybb2基因敲除小鼠模型建立后,经Western blot鉴定,纯合小鼠晶体蛋白未检测到Crybb2的表达,杂合及野生型小鼠晶体蛋白在分子量23KD处检测到该蛋白的表达。
2.Crybb2基因敲除导致小鼠白内障的发生,白内障均发生在前或后皮质部,最早发生于出生后8周左右。Crybb2定位于晶状体皮质囊膜下,基因敲除后,晶状体抗氧化能力下降,随年龄增加,皮质变薄。
3.P-ERG检查发现Crybb2基因敲除小鼠振幅降低。野生型小鼠视网膜,大脑,脊髓,睾丸,卵巢中可检测到Crybb2 mRNA,Crybb2阳性表达。Crybb2基因敲除后,精子活力下降,计数减少,小鼠睾丸和卵巢外观减小,睾丸重量减轻。小鼠生仔数目轻度减少,窝数减少。
结论:
1.Crybb2基因敲除可以导致C57BL/C小鼠白内障的发生,为皮质性白内障,皮质混浊程度随年龄增加而增加,皮质厚度随年龄的增加而变薄。
2.Crybb2基因敲除可以降低C57BL/C小鼠生殖功能。
Crystallins,membrane protein and cytosteletal protein are the main compositon proteins of the len.Crystallins is water-soluble,but cytosteletal protein and membrane protein and polymerized crystallins are urea-soluble.90%of the water-soluble proteins in the heman eye lens are the crystallins:α、βandγcrystallin.
The study of the function ofα-crystallin is widespread and the molecular chaperone of it was generally accepted.But the study toβ-crystallin is ralatively less. The concentration ofβB2-crystallin is not only higher than otherβ-crystallin but also increase with age.So the function of it is deserved to research.
Crystallin gene knockout is an important method to study the function of crystallin.Some research have find that theα-crystallin gene knockout can lead to cataract,so do theαorβ-crystallin gene mutation.It has not been reported the animal model ofβB2-crystallin gene knock out all over the world.So we chose the crystallin as the target and set up the animal model so as to research its function on maintaining the transparency of lens and its extralenticular functions.
In our study,pattern electroretinogram was used to study the function of retinal ganglion cell after the gene knock out.The lens ofβB2-crystallin gene knockout mice was studied in this article.We examined the in vitro construction of len and analysis the function ofβB2-crystallin in keeping transparency of the lens and observed influence on reproduction of the mouse with targeted knockout of the mouseβB2-crystallin gene compared with the wild tipe.
Methods:
1.Generation and verification ofβB2-crystallin gene knockout mice.
βB2-crystallin gene knockout mice were produced by the in Genious Targeting Laboratory.The model of mice were 10 heterozygote which have been breed in the central lab and have reproduced over 30 generations.Gene expression were characterized by PCR and western blot.
2.The structure and character of lens inβB2-crystallin gene knockout mice
Fresh lens from 8-week-old gene knockout and wild type mice were removed from the eyeballs and cultured in TC-199 medium for 2 hours in a CO_2 incubator,and then the gene knockout mice were screened for the degree of opacity with dark field biomicroscopy.Microstructure of lens was analyzed by hematoxylin and eosin stain and immunohistochemistry.By studying cortex of different ageβB2-crystallin gene knockout mice lens,we observed the influence to development of cataract.
3.Fertility were studied using knock out ofβB2-crystallin mice and the wild type
Pattern electroretinogram was used to study the function of retinal ganglion cell after the gene knock out.We used Western Blot,PCR and immunohistochemistry to detect mRNA ofβB2-crystallin gene,βB2-crystallin outside the len(retina,brain, spinal cord,ovary and testis) although it was expressed at lower levels in several extralenticular locations.Through the babies of the mouse cipher,Sperm count,testis weigh,using morphshape and hematoxylin and eosin stain observation method,we studied the reproduction function of the mice of targeted knockout of the mouseβB2-crystallin gene compared with the wild tipe.
RESULTS:
1.Western blot failed to detect anyβB2-crystallin in the lens ofβB2-crystallin gene knockout mice.
2.The gene knockout mice were screened more severe opacity with dark field biomicroscopy.Hematoxylin and eosin stain and immunohistochemistry found that theβB2-crystallin was located in subcapsular of the cortex and the cortex was thiner in the gene knockout mice with ageing.
3.The vibration of the Pattern electroretinogram was lower after gene knock out. Through the mice the baby cipher,Sperm count,testis weigh,we found that the productivity were lower in the gene knock mice.Using morphshape and hematoxylin and eosin stain,we observed smller shape and structure chaos in the mice with targeted knockout of theβB2-crystallin gene compared with the wild tipe.
Conclusions:
1.Targeted knockout of the mouseβB2-crystallin gene can induce cataract which is located in the subcapsular,and then the cortex of the lens grow thinner with age.
2.Targeted knockout of the mouseβB2-crystallin gene induces subfertility
目前对α-晶体蛋白的功能研究比较广泛,它的分子伴侣作用已得到世界公认。对β-晶体蛋白的研究还比较少,其中βB2晶体蛋白(βB2 crystallin,Crybb2)在β族晶体蛋白中含量最高,而且它的水溶性成分呈年龄依赖性增高,因此,它的正常结构及其水溶性成分水平,对维持晶状体的高折射系数和透明至关重要。这种反常性增高势必包含了它在维持晶状体透光性中的重要作用,因此它的功能值得进一步研究。
基因敲除是研究蛋白功能的一个重要手段,已有研究证明α-晶体蛋白基因敲除可以导致白内障,而且α或β-晶体蛋白基因突变也可以导致白内障。文献报道Crybb2基因突变可降低生殖功能。目前国内外尚未有Crybb2基因敲除动物模型的报道,因此我们选择此蛋白作为靶点,利用Crybb2基因敲除小鼠模型,来研究该蛋白在维持晶状体透明性中的作用和其晶状体外生物学功能。
本文主要通过观察Crybb2基因敲除对小鼠晶状体结构的影响及其在晶状体内和晶状体外组织的定位,分析该蛋白在维持晶状体透明性中的作用并研究其晶状体外功能。
主要方法:
1.Crybb2基因敲除小鼠模型的建立及鉴定
此部分工作是应第二军医大学第一附属医院中心实验室要求,与美国纽约iGTL实验室合作并最终在美国iGTL实验室完成,最后以馈赠方式供我们研究专用。小鼠品系为C57BL/C小鼠,小鼠模型为10只杂合子,已成功进行繁殖超过30代,子代小鼠生长发育状况良好。
取鼠尾末端组织,通过PCR技术对小鼠基因型进行鉴定;取小鼠眼晶状体进行匀浆离心后取上清液,通过Western blot技术对晶体蛋白的表达进行鉴定。鉴定后将小鼠分类饲养繁殖。
2.Crybb2基因敲除小鼠晶状体结构特征
用暗视野显微镜观察经氧化损伤后晶状体体外培养的混浊程度。HE染色观察晶状体囊膜下皮质的厚度随年龄的变化,并与野生型同品系小鼠对比。免疫组织化学研究其在晶状体内的定位。
3.Crybb2基因敲除小鼠晶状体外功能研究
图形视网膜电图(pattern electroretinogram,P-ERG)研究Crybb2基因敲除后视觉电生理的改变。Western Blot,PCR和免疫组织化学方法检测Crybb2 mRNA,Crybb2在晶状体外阳性表达(视网膜、大脑、脊髓、睾丸、卵巢),尽管是低水平表达。数小鼠产仔数,精子计数,睾丸称重,大体形态和HE染色观察形态学改变研究Crybb2基因敲除后小鼠生殖功能的改变,并与野生型同品系小鼠对比。
实验结果:
1.Crybb2基因敲除小鼠模型建立后,经Western blot鉴定,纯合小鼠晶体蛋白未检测到Crybb2的表达,杂合及野生型小鼠晶体蛋白在分子量23KD处检测到该蛋白的表达。
2.Crybb2基因敲除导致小鼠白内障的发生,白内障均发生在前或后皮质部,最早发生于出生后8周左右。Crybb2定位于晶状体皮质囊膜下,基因敲除后,晶状体抗氧化能力下降,随年龄增加,皮质变薄。
3.P-ERG检查发现Crybb2基因敲除小鼠振幅降低。野生型小鼠视网膜,大脑,脊髓,睾丸,卵巢中可检测到Crybb2 mRNA,Crybb2阳性表达。Crybb2基因敲除后,精子活力下降,计数减少,小鼠睾丸和卵巢外观减小,睾丸重量减轻。小鼠生仔数目轻度减少,窝数减少。
结论:
1.Crybb2基因敲除可以导致C57BL/C小鼠白内障的发生,为皮质性白内障,皮质混浊程度随年龄增加而增加,皮质厚度随年龄的增加而变薄。
2.Crybb2基因敲除可以降低C57BL/C小鼠生殖功能。
Crystallins,membrane protein and cytosteletal protein are the main compositon proteins of the len.Crystallins is water-soluble,but cytosteletal protein and membrane protein and polymerized crystallins are urea-soluble.90%of the water-soluble proteins in the heman eye lens are the crystallins:α、βandγcrystallin.
The study of the function ofα-crystallin is widespread and the molecular chaperone of it was generally accepted.But the study toβ-crystallin is ralatively less. The concentration ofβB2-crystallin is not only higher than otherβ-crystallin but also increase with age.So the function of it is deserved to research.
Crystallin gene knockout is an important method to study the function of crystallin.Some research have find that theα-crystallin gene knockout can lead to cataract,so do theαorβ-crystallin gene mutation.It has not been reported the animal model ofβB2-crystallin gene knock out all over the world.So we chose the crystallin as the target and set up the animal model so as to research its function on maintaining the transparency of lens and its extralenticular functions.
In our study,pattern electroretinogram was used to study the function of retinal ganglion cell after the gene knock out.The lens ofβB2-crystallin gene knockout mice was studied in this article.We examined the in vitro construction of len and analysis the function ofβB2-crystallin in keeping transparency of the lens and observed influence on reproduction of the mouse with targeted knockout of the mouseβB2-crystallin gene compared with the wild tipe.
Methods:
1.Generation and verification ofβB2-crystallin gene knockout mice.
βB2-crystallin gene knockout mice were produced by the in Genious Targeting Laboratory.The model of mice were 10 heterozygote which have been breed in the central lab and have reproduced over 30 generations.Gene expression were characterized by PCR and western blot.
2.The structure and character of lens inβB2-crystallin gene knockout mice
Fresh lens from 8-week-old gene knockout and wild type mice were removed from the eyeballs and cultured in TC-199 medium for 2 hours in a CO_2 incubator,and then the gene knockout mice were screened for the degree of opacity with dark field biomicroscopy.Microstructure of lens was analyzed by hematoxylin and eosin stain and immunohistochemistry.By studying cortex of different ageβB2-crystallin gene knockout mice lens,we observed the influence to development of cataract.
3.Fertility were studied using knock out ofβB2-crystallin mice and the wild type
Pattern electroretinogram was used to study the function of retinal ganglion cell after the gene knock out.We used Western Blot,PCR and immunohistochemistry to detect mRNA ofβB2-crystallin gene,βB2-crystallin outside the len(retina,brain, spinal cord,ovary and testis) although it was expressed at lower levels in several extralenticular locations.Through the babies of the mouse cipher,Sperm count,testis weigh,using morphshape and hematoxylin and eosin stain observation method,we studied the reproduction function of the mice of targeted knockout of the mouseβB2-crystallin gene compared with the wild tipe.
RESULTS:
1.Western blot failed to detect anyβB2-crystallin in the lens ofβB2-crystallin gene knockout mice.
2.The gene knockout mice were screened more severe opacity with dark field biomicroscopy.Hematoxylin and eosin stain and immunohistochemistry found that theβB2-crystallin was located in subcapsular of the cortex and the cortex was thiner in the gene knockout mice with ageing.
3.The vibration of the Pattern electroretinogram was lower after gene knock out. Through the mice the baby cipher,Sperm count,testis weigh,we found that the productivity were lower in the gene knock mice.Using morphshape and hematoxylin and eosin stain,we observed smller shape and structure chaos in the mice with targeted knockout of theβB2-crystallin gene compared with the wild tipe.
Conclusions:
1.Targeted knockout of the mouseβB2-crystallin gene can induce cataract which is located in the subcapsular,and then the cortex of the lens grow thinner with age.
2.Targeted knockout of the mouseβB2-crystallin gene induces subfertility
引文
[1]葛坚,赵家良,崔浩.2005年8月第一版 眼科学.209.
[2]Bloemendal H,de Jong W,Jaenicke R,et al.Ageing and vision:structure,stability and function of lens crystallins.Progress in Biophysics & Molecular Biology.2004,86:407-485.
[3]李闻捷,Joseph-Fu S-C.βB2-晶体蛋白对眼晶体老化的影响.中国病理生理杂志.2004,20:1905-1907.
[4]李闻捷,Joseph-Fu S-C.大鼠主要水溶性晶体蛋白在老化进程中的时相变化中国病理生理杂志.2004,20:22-26.
[5]张军,黄才国,李闻捷等.β B2-晶体蛋白基因敲除小鼠模型的建立.第二军医大学学报.2006,27:1246-1248.
[6]James P Brady,Donita Garland,Yvonne Duglas-Tabor,et al.Targeted disruption of the mouse αA-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein αB-crystallin.Proc Natl Acad Sci.1997,94:884-889.
[7]Boyle DL,Takemoto L,Brady JP,et al.Morphological characterization of the α-A and α-B crystallin double knockout mouse lens.BMC Ophthalmol.2003,3:3.
[8]Brady JP,Garland,et al.Targeted disruption of the mouse alphaA-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein alphaB-crystallin.Proc.Natl.Acad.Sci.1997,94:884-889.
[9]Brady JP,Garland DL,Green DE,et al.AlphaB-crystallin in lens development and muscle integrity:a gene knockout approach.Invest.ophathalmol.Vis.Sci.2001,42:2924-2934.
[10]Chambers C,Russell P.Deletion mutation in an eye lens beta-crystallin.An animal model for inherited cataracts.J Biol Chem.1991,266:6742-6746.
[11]Graw J,L(o|¨)ster J,Soewarto D,et al.Aey2,a new mutation in the betaB2-crystallin-encoding gene of the mouse.Invest Ophthalmol Vis Sci.2001,42:1574-1580.
[12]Yao K,Tang X,Shentu X,et al.Progressive polymorphic congenital cataract caused by a CRYBB2 mutation in a Chinese family.Mol Vis.2005,11:758-763.
[13]Pauli S,S(o|¨)ker T,Klopp N,et al.Mutation analysis in a German family identified a new cataract-causing allele in the CRYBB2 gene.Mol Vis.2007,13:962-967.
[14]Wang K,Spector A.Alpha-crystallin can as chaperone under condition of oxidative stress.Invest Ophthalmol Vis Sci.1995,36:311.
[15]Ueda Y,Duncan MK,David LL.Lens proteomics:the accumulation of crystallin modifications in the mouse lens with age.Invest Ophthalmol Vis Sci.2002,43:205-215.
[16]Thomas Liedtke Jen,Christian Schwamborn,Uwe Schroer et al.Elongation of Axons during Regeneration Involves Retinal Crystallin βb2(crybb2).Molecular &Cellular Proteomics.2007,6:895-907.
[17]Kevin M.DuPrey,Kimberly M.Robinson,et al.Subfertility in mice harboring a mutation in β B2-crystallin.Molecular Vision.2007,13:366-373.
[19]Magabo KS,Horwitz J,Piatigorsky J,et al.Kantorow M.Expression of betaB (2)-crystallin mRNA and protein in retina,brain,and testis.Invest Ophthalmol Vis Sci.2000,41:3056-60.
[18]Fang Bai,Jing-hua Xi,Usha P.Andley.Up-regulation of tau,a brain microtubule-associated protein,in lens cortical fractions of aged αA-,αB-,and αA/B-crystallin knockout mice.Mol Vis.2007;13:1589-1600.
[20]Head M W,Sedowofia,K,and Clayton,R.M.βB2-crystallin in the mammalian retina.Exp.Eye Res.1995 61,423-428.
[21]Crabb J W,Miyagi,M,Gu,X,et al.Drusen proteome analysis:an approach to the etiology of age-related macular degeneration.Proc.Natl.2002,99,14682-14687.
[22]同济医科大学/中山医科大学病理学教研室 外科病理学.705-719.
[23]刘梦蕾,李闻捷,蔡刚等.SD大鼠βB2-晶体蛋白的克隆、表达与纯化.现代临床医学生物工程学杂志.2005,11(1):1-3.
[1]Francois J.Genetics of cataract.Ophthalmologica.1982,184:61-71.
[2]Merin S.Inherited cataracts.Inherited eye diseases.New York:Marcel Dekker,Inc.1991,86-120.
[3]Haargaard B,Wohlfahrt J,Fledelius HC,Rosenberg T,Melbye M.A nationwide Danish study of 1027 cases of congenital/infantile cataracts:etiological and clinical classifications.Ophthalmology.2004,111:2292-2298.
[4]布娟,赵堪兴.先天性白内障分子发病机制的研究进展.国际眼科杂志,2005,5(4):973-977。
[5]温克征.先天性白内障病因新进展.中国医学文摘.儿科学,2007,26(1):1-3.
[6]雄壮,冷非.先天性白内障的分类及致病基因研究进展.中国斜视与小儿眼科杂志,2008,16(2):94-96。
[7]杨帆,孙慧敏.先天性白内障的分子遗传学研究及其相关表现型.天津医科大学学报.2006,12(1):137-141。
[8]Santhiya ST,Shyam MM,Rawlley D,et al.Novel mutations in the gamma-crystallin genes cause autosomal dominant congenital cataracts.J Med Genet,2002,339:352.
[9]Rees MI,Watts P,Fenton I,et al.Further evidence of autosomal dominant congenital zonular pulverulent cataracts linked to 13q11(CZP3) and a novel mutation in connexin 46(GJA3).Hum Genet,2000,106:206.
[10]Polyakov AV,Shagina IA,Khlebnikova OV,et al.Mutation in the connexin 50gene(GJA8) in a Russian family with zonular pulverulent cataract.Clin Genet,2001,60:476.
[11]Berry V,Mackay D,Khaliq S,et al.Connexin 50 mutation in a family with congenital "zonular nuclear "pulverulent cataract of Pa-kistani origin.Hum Genet,1999,105(122):168-170.
[12]Vanita,Sarhadi V,Reis A,et al.A unique form of autosomal dominant cataract explained by gene conversion between beta-crystallin B2 and its pseudogene.J Med Genet,2001,38:392.
[13]Santhiya ST,Shyam MM,Rawlley D,et al.Novel mutations in the gamma-crystallin genes cause autosomal dominant congenital cataracts.J Med Genet,2002,39:352.
[14]Berry V,Francis P,Kaushal S,et al.Missense mutationsin MIP underlie autosomal dominant'polymorphic'and lamellar cataracts linked to 12q.Nat Genet,2000,25:15.
[15]Conley YP.Erturk D,Keverline A,et al.A juvenile-onset,progressive cataract locus on chromosome 3q21-q22 is associated with a missense mutation in the beaded filament structural protein-2.Am J Hum Genet,2000,66:1426.
[16]Berry V,Ionides ACW,Moore AT,et al.Alocus for autosomal dominant anterior polar cataract on chromosome 17p.Hum Molec Genet,1996,5:415-419.
[17]Berry V,Francis P,Reddy MA,et al.Alpha-B crystallin gene(CRYAB)mutation causes dominant congenital posterior polar cataract in humans.Am J Hum Genet,2001,69:1141.
[18]Bu L,Jin Y,Shi Y,et al.Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract.Nat Genet,2002,31:276.
[19]Vanita,Singh JR,Sarhadi VK,et al.Anovel form of "central pouch like"cataract,with suturalo pacities,mapsto chromosome 15q21-22.Am J Hum Genet,2001,68(2):509-514.
[20]谷静芝,阮燕飞,李响等.花冠状常染色体显性遗传性先天性白内障致病基因初步定位.眼科进展,2008,28(8):565-865。
[21]Nandrot E,Slingsby C,Basak A,et al.Gamma-Dcrystallin gene(CRYGD)mutation causes autosomal dominant congenital cerulean cataracts.J Med Genet,2003,40(4):262-267.
[22]Gill D,Klose R,Munier FL,et al.Genetichetero geneity of the Coppock-like cataract:amutation in CRYBB2 on chromosome 22q11.2.Invest Ophthalmol Vis Sci,2000,41(1):159-165.
[23]Heon E,Paterson A D,Fraser M,et al.A progressive autosomal recessive cataract locus maps to chromosome 9q13-q22.Am J Hum Genet,2001,68:772-777.
[24]Francis PJ,Berry B,Hardcastle AJ,et al.A locus for isolated cataract on human Xp.J Med Genet,2002,39:105-109.
[25]何守志.晶状体病学.北京:人民卫生出版社,2004:27-30.
[26]李妮,刘谊.常染色体显性先天性白内障的基因定位与克隆.眼科研究,2005,23(1):100-103.
[27]Wang Jun,Ma Xu,Gu Feng,et al.A missense mutation S228P in the CRYBB1gene causes autosomal dominant congenital cataract.Chin Med J,2007,120(9):820.
[28]Santhiya ST,Shyam Manohar M,Rawlley D,et al.Novel mutations in the gamma-crystallin gene cause autosomal dominant congenital cataracts.J Med Genet,2002,39(5):352-8.
[29]汤霞靖,姚克.晶体蛋白基因与先天性白内障.国外医学眼科学分册,2004,28(6):374-377。
[30]齐艳华,贾红艳,黄尚志等.晶体蛋白βA1基因缺失突变导致常染色体显性遗传核性先天性白内障.中华医学遗传学杂志,2003,20(6):486-489。
[31]齐艳华,马兰茗.晶体蛋白βB2基因突变导致常染色体显性遗传先天性白内障.眼科新进展,2008,28(9):676-876。
[32]Lu S,Zhao C,Jiao H,et al.Two Chinese families with pulverulent congenital cataracts and delta G91 CRYBA1 mutations.Mol Vis,2007,13:1154-1160.
[33]Wang J,Ma X,Gu F,et al.A missense mutation S228P in the CRYBB1 gene causes autosomal dominant congenital cataract.Chin Med J(Engl),2007,120(9):820-824.
[34]Liu M,Ke T,Wang Z,et al.Identification of a CRYAB mutation associated with autosomal dominant posterior polar cataract in a Chinese family.Invest Ophthalmol Vis Sci,2006,47(8):3461-3466.
[35]Cobb BA,Petrash JM.Structural and functional changes in the alpha-A-crystallin R116C mutant in hereditary cataracts.Biochemistry,2000,39:15791-15798.
[36]Berry V,Francis P,Reddy MA.Alpha-B crystallin gene(CRYAB) mutation causes dominant congenital posterior polar cataract in humans.Am J Hum Genet,2001,69:1141-1145.
[37]Santhiya ST,Soker T,Klopp N,et al.Identification of a novel,putative cataract-causing allele in CRYAA(G98R)in an Indian family.Mol Vis,2006,12:768-773.
[38]Berry V,Francis P,Reddy MA,et al.Alpha-B crystallin gene(CRYAB)mutation causes dominant congenital posterior polar cataract in humans.Am J Hum Genet.2001,69(5):1141-1145.
[39]Qi Y,Jia H,Huang S,et al.A deletion mutation in the betaA1/A3 crystallin gene(CRYBA1/A3)is associated with autosomal dominant congenital nuclear cataract in a Chinese family.Hum Genet,2004,114(2):192-197.
[40]Santhiya ST,Manisastry SM,Rawlley D,et al.Mutation analysis of congenital cataracts in Indian families:identification of SNPS and a new causative allele in CRYBB2 gene.Invest Ophthalmol Vis Sci,2004,45(10):3599-3607.
[41]Willoughby CE,Shafiq A,Ferrini W,et al.CRYBB1 mutation associated with congenital cataract and microcomea.Mol Vis,2005,11:587-593.
[42]Xu WZ,Zheng S,Xu SJ,et al.Autosomal dominant coralliform cataract related to a missense mutation of the gamma D-crystallin gene.Chin Med J(Engl),2004,117(5):727-732.
[43]Gonzalez Huerta LM,Messina Baas OM,Cuevas Covarrubias SA.A family with autosomal dominant primary congenital cataract associated with a CRYGC mutation:evidence of clinical heterogeneity.Mol Vis,2007,13:1333-1338.
[44]Sun H,Ma Z,Li Y,et al.Gamma-S crystallin gene(CRYGS)mutation Causes dominant progressive cortical cataract in humans.J Med Genet,2005,42(9):706-710.
[45]林辉,王丽,周南,等.晶状体膜蛋白MIP基因C末端一个新的错义突变导致双眼多形性先天性白内障.中华医学遗传学杂志,2008,25(1):6-10。
[46]林婴,刘妮妮,雷春涛,等.一个先天性白内障家系缝隙连接蛋白基因新突变.中华医学遗传学杂志,2008,25(1):59-62。
[47]林英,郑建秋,刘平.先天性白内障与缝隙连接蛋白Cx50.国际眼科杂志,2007,7(6):1658-1661。
[48]Guleria K,Sperling K,Singh D,et al.A novel mutation in the connexin 46(GJA3)gene associated with autosomal dominant congenital cataract in an Indian family.Mol Vis,2007,13:1657-1665.
[49]Vanita V,Hennies HC,Singh D,et al.A novel mutation in GJA8 associated with autosomal dominant congenital cataract in a family of Indian origin.Mol Vis,2006,12:1217-1222.
[50]Gu F,Zhai H,Li D,et al.A hovel mutation in major intrinsic protein of the Iens gene(MIP)underlies autosomal dominant cataract in a Chinese family.Mol Vis,2007,13:1651-1656.
[51]夏欣一,杨滨,崔英霞,等。常染色体显性先天性白内障致病基因研究进展。中国优生与遗传杂志.2008,16(6):10-12。
[52]Semina EV,Ferrell RE,Mintz-Hittner HA.A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD.Nature Genet,1998,19:167-170
[53]Addison PK,Berry V,Ionides AC.Posterior polar cataract is the predominant consequence of a recurrent mutation in the PITX3 gene.Br J Ophthalmol,2005,89(2):138-141.
[54]Jordan T,Hanson I,Zaletayev D.The human PAX6 gene is mutated in two patients with aniridia.Nature Genet,1992,1:328-332.
[55]Burdon KP,McKay JD,Wirth MG,et al.The PITX3 gene in posterior polar congenital cataract in Australia.Mol Vis,2006,12:367-371.
[56]葛坚.眼科学.北京:人民卫生出版社,2005:219-221.
[57]曹志红,李杨.转录调节因子基因突变与先天性白内障.国际眼科纵览,2007,31(2):92-95.
[58]Ke T,Wang QK,Ji B,et al.Novel HSF4 mutation causes congenital total white cataract in a Chinese family.Am J Ophthalmol,2006,142(2):298-303.
[59]Perveen R,Favor J,Jamieson RV,et al.A heterozygous c-Maf transactivation domain mutation causes congenital cataractand enhances target gene activation.Htim Mol Genet,2007,16(9):1030-1038.
[60]Vanita V Singh D,Robinson PN,Sperling K,et al.A novel mutation in the DNA-binding domain of MAF at 16q23.1 associated with autosomal dominant “cerulean cataract” in an Indian family.Am J Med Genet A,2006,140(6):558-566.
[1]Klein BE,Klein R,Lee KE.Incidence of age-related cataract over a 10-year interval:the Beaver Dam Eye Study.Ophthalmology.2002,109:2052-2057.
[2]H.Bloemendal et al.Ageing and vision:structure,stability and function of lens crystallins.Progress in Biophysics & Molecular Biology 2004,86:407-485.
[3]Sonna LA,Fujita J,Gaffin SL,et al.Invited review:effects of heat and cold stress on mammalian gene expression.J.Appl.Physiol 2002,92:1725-1742.
[4]Csermely P.Chaperone overload is a possible contributor to civilization diseases.Trends Genet.2001,17:701-704.
[5]Magabo KS,Horwitz J,Piatigorsky J,et al.Expression of betaB (2)-crystallin mRNA and protein in retina,brain,and testis.Invest Ophthalmol Vis Sci.2000,41:3056-3060.
[6]Michael R,van Marie J,Vrensen GF,et al.Changes in the refractive index of lens fibre membranes during maturation—impact on lens transparency.Exp Eye Res.2003,77:93-99.
[7]Franceschi C,Valensin S,Bonafe M,et al.The network and the remodeling theories of aging:historical background and new perspectives.Exp.Gerontol.2000,35:879-896.
[8]Kmoch S,Brynda J,Asfaw B,et al.Link between a novel human gammaD-cirystallin allele and a unique cataract phenotype explained by protein crystallography.Hum.Mol.Genet 2000,9:1779-1786.
[9]Patil C,Walter P.Intracellular signaling from the endoplasmic reticulum to the nucleus:the unfolded protein response in yeast and mammals.Cell Biol.2001,13:349-355.
[10]Alizadeh A,Clark JI,Seeberger T,et al.Targeted genomic deletion of the lens-specific intermediate filament protein CP49.Invest.Ophthalmol.Vis.Sci.2002,43:3722-3727.
[11]Michael R,van Marie J,Vrensen GF,et al.Changes in the refractive index of lens fibre membranes during maturation-impact on lens transparency.Exp.Eye Res.2003,77:93-99.
[12]Ueda Y,Duncan MK,David L.Lens proteomics:the accumulation of crystallin modifications in the mouse lens with age.Invest Ophthalmol Vis Sci.2002,43:205-215.
[13]Smith G,Atchison DA,Pierscionek BK.Modeling the power of the aging human eye.J.Opt.Soc.Am.A 1992,9:2111-2117.
[14]Ma ZX,Hanson SRA,Lampi KJ,et al.Age-related changes in human lens crystallins identified by HPLC and mass spectrometry.Exp.Eye.Res 1998,67:21-30.
[15]Bateman,JB,FR yon-Bischhoff,L.Richter,et al.Gene conversion mutation in crystallin,beta-B2 (CRYBB2) in a Chilean family with autosomal dominant cataract.Ophthalmology,2007,114:425-32.
[16]Lampi KJ,Shih M,Ueda Y,et al.Lens proteomics:analysis of rat crystallin sequences and two-dimensional electrophoresis map.Invest.Ophthalmol.Vis.Sci 2002,43:216-224.
[17]Nandrot E,Slingsby C,Basak A,et al.Gamma-D crystallin gene(CRYGD) mutation causes autosomal dominant congenital cerulean cataracts.J Med Genet,2003,40:262-267.
[18]Wistow G,Bernstein SL,Wyatt MK,et al.Expressed sequence tag analysis of adult human lens for the NEIBank Project:over 2000 non-redundant transcripts,novel genes and splice variants.Mol.Vis 2002,8:171-184.
[19]Shen T X,Yao K,Xu W,et al.Special fasciculiform caused by a mutuation in the y-D crystallin gene.Mol.Vis 2004,10:233-239.
[20]Nijveen H,Civil A,Van Genesen ST,et al.Regulatory elements in the rat beta B2-crystallin promoter.Exp.Eye Res.2001,73:703-710.
[21]Thomas L Jen,Christian S,Uwe Schroer et al.Elongation of Axons during Regeneration Involves Retinal Crystallin |3b2 (crybb2).Molecular & Cellular Proteomics.2007,6:895-907.
[22]Kevin M.DuPrey,Kimberly M.Robinson,et al.Subfertility in mice harboring a mutation in PB2-crystallin.Molecular Vision,2007,13:366-373.
[2]Bloemendal H,de Jong W,Jaenicke R,et al.Ageing and vision:structure,stability and function of lens crystallins.Progress in Biophysics & Molecular Biology.2004,86:407-485.
[3]李闻捷,Joseph-Fu S-C.βB2-晶体蛋白对眼晶体老化的影响.中国病理生理杂志.2004,20:1905-1907.
[4]李闻捷,Joseph-Fu S-C.大鼠主要水溶性晶体蛋白在老化进程中的时相变化中国病理生理杂志.2004,20:22-26.
[5]张军,黄才国,李闻捷等.β B2-晶体蛋白基因敲除小鼠模型的建立.第二军医大学学报.2006,27:1246-1248.
[6]James P Brady,Donita Garland,Yvonne Duglas-Tabor,et al.Targeted disruption of the mouse αA-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein αB-crystallin.Proc Natl Acad Sci.1997,94:884-889.
[7]Boyle DL,Takemoto L,Brady JP,et al.Morphological characterization of the α-A and α-B crystallin double knockout mouse lens.BMC Ophthalmol.2003,3:3.
[8]Brady JP,Garland,et al.Targeted disruption of the mouse alphaA-crystallin gene induces cataract and cytoplasmic inclusion bodies containing the small heat shock protein alphaB-crystallin.Proc.Natl.Acad.Sci.1997,94:884-889.
[9]Brady JP,Garland DL,Green DE,et al.AlphaB-crystallin in lens development and muscle integrity:a gene knockout approach.Invest.ophathalmol.Vis.Sci.2001,42:2924-2934.
[10]Chambers C,Russell P.Deletion mutation in an eye lens beta-crystallin.An animal model for inherited cataracts.J Biol Chem.1991,266:6742-6746.
[11]Graw J,L(o|¨)ster J,Soewarto D,et al.Aey2,a new mutation in the betaB2-crystallin-encoding gene of the mouse.Invest Ophthalmol Vis Sci.2001,42:1574-1580.
[12]Yao K,Tang X,Shentu X,et al.Progressive polymorphic congenital cataract caused by a CRYBB2 mutation in a Chinese family.Mol Vis.2005,11:758-763.
[13]Pauli S,S(o|¨)ker T,Klopp N,et al.Mutation analysis in a German family identified a new cataract-causing allele in the CRYBB2 gene.Mol Vis.2007,13:962-967.
[14]Wang K,Spector A.Alpha-crystallin can as chaperone under condition of oxidative stress.Invest Ophthalmol Vis Sci.1995,36:311.
[15]Ueda Y,Duncan MK,David LL.Lens proteomics:the accumulation of crystallin modifications in the mouse lens with age.Invest Ophthalmol Vis Sci.2002,43:205-215.
[16]Thomas Liedtke Jen,Christian Schwamborn,Uwe Schroer et al.Elongation of Axons during Regeneration Involves Retinal Crystallin βb2(crybb2).Molecular &Cellular Proteomics.2007,6:895-907.
[17]Kevin M.DuPrey,Kimberly M.Robinson,et al.Subfertility in mice harboring a mutation in β B2-crystallin.Molecular Vision.2007,13:366-373.
[19]Magabo KS,Horwitz J,Piatigorsky J,et al.Kantorow M.Expression of betaB (2)-crystallin mRNA and protein in retina,brain,and testis.Invest Ophthalmol Vis Sci.2000,41:3056-60.
[18]Fang Bai,Jing-hua Xi,Usha P.Andley.Up-regulation of tau,a brain microtubule-associated protein,in lens cortical fractions of aged αA-,αB-,and αA/B-crystallin knockout mice.Mol Vis.2007;13:1589-1600.
[20]Head M W,Sedowofia,K,and Clayton,R.M.βB2-crystallin in the mammalian retina.Exp.Eye Res.1995 61,423-428.
[21]Crabb J W,Miyagi,M,Gu,X,et al.Drusen proteome analysis:an approach to the etiology of age-related macular degeneration.Proc.Natl.2002,99,14682-14687.
[22]同济医科大学/中山医科大学病理学教研室 外科病理学.705-719.
[23]刘梦蕾,李闻捷,蔡刚等.SD大鼠βB2-晶体蛋白的克隆、表达与纯化.现代临床医学生物工程学杂志.2005,11(1):1-3.
[1]Francois J.Genetics of cataract.Ophthalmologica.1982,184:61-71.
[2]Merin S.Inherited cataracts.Inherited eye diseases.New York:Marcel Dekker,Inc.1991,86-120.
[3]Haargaard B,Wohlfahrt J,Fledelius HC,Rosenberg T,Melbye M.A nationwide Danish study of 1027 cases of congenital/infantile cataracts:etiological and clinical classifications.Ophthalmology.2004,111:2292-2298.
[4]布娟,赵堪兴.先天性白内障分子发病机制的研究进展.国际眼科杂志,2005,5(4):973-977。
[5]温克征.先天性白内障病因新进展.中国医学文摘.儿科学,2007,26(1):1-3.
[6]雄壮,冷非.先天性白内障的分类及致病基因研究进展.中国斜视与小儿眼科杂志,2008,16(2):94-96。
[7]杨帆,孙慧敏.先天性白内障的分子遗传学研究及其相关表现型.天津医科大学学报.2006,12(1):137-141。
[8]Santhiya ST,Shyam MM,Rawlley D,et al.Novel mutations in the gamma-crystallin genes cause autosomal dominant congenital cataracts.J Med Genet,2002,339:352.
[9]Rees MI,Watts P,Fenton I,et al.Further evidence of autosomal dominant congenital zonular pulverulent cataracts linked to 13q11(CZP3) and a novel mutation in connexin 46(GJA3).Hum Genet,2000,106:206.
[10]Polyakov AV,Shagina IA,Khlebnikova OV,et al.Mutation in the connexin 50gene(GJA8) in a Russian family with zonular pulverulent cataract.Clin Genet,2001,60:476.
[11]Berry V,Mackay D,Khaliq S,et al.Connexin 50 mutation in a family with congenital "zonular nuclear "pulverulent cataract of Pa-kistani origin.Hum Genet,1999,105(122):168-170.
[12]Vanita,Sarhadi V,Reis A,et al.A unique form of autosomal dominant cataract explained by gene conversion between beta-crystallin B2 and its pseudogene.J Med Genet,2001,38:392.
[13]Santhiya ST,Shyam MM,Rawlley D,et al.Novel mutations in the gamma-crystallin genes cause autosomal dominant congenital cataracts.J Med Genet,2002,39:352.
[14]Berry V,Francis P,Kaushal S,et al.Missense mutationsin MIP underlie autosomal dominant'polymorphic'and lamellar cataracts linked to 12q.Nat Genet,2000,25:15.
[15]Conley YP.Erturk D,Keverline A,et al.A juvenile-onset,progressive cataract locus on chromosome 3q21-q22 is associated with a missense mutation in the beaded filament structural protein-2.Am J Hum Genet,2000,66:1426.
[16]Berry V,Ionides ACW,Moore AT,et al.Alocus for autosomal dominant anterior polar cataract on chromosome 17p.Hum Molec Genet,1996,5:415-419.
[17]Berry V,Francis P,Reddy MA,et al.Alpha-B crystallin gene(CRYAB)mutation causes dominant congenital posterior polar cataract in humans.Am J Hum Genet,2001,69:1141.
[18]Bu L,Jin Y,Shi Y,et al.Mutant DNA-binding domain of HSF4 is associated with autosomal dominant lamellar and Marner cataract.Nat Genet,2002,31:276.
[19]Vanita,Singh JR,Sarhadi VK,et al.Anovel form of "central pouch like"cataract,with suturalo pacities,mapsto chromosome 15q21-22.Am J Hum Genet,2001,68(2):509-514.
[20]谷静芝,阮燕飞,李响等.花冠状常染色体显性遗传性先天性白内障致病基因初步定位.眼科进展,2008,28(8):565-865。
[21]Nandrot E,Slingsby C,Basak A,et al.Gamma-Dcrystallin gene(CRYGD)mutation causes autosomal dominant congenital cerulean cataracts.J Med Genet,2003,40(4):262-267.
[22]Gill D,Klose R,Munier FL,et al.Genetichetero geneity of the Coppock-like cataract:amutation in CRYBB2 on chromosome 22q11.2.Invest Ophthalmol Vis Sci,2000,41(1):159-165.
[23]Heon E,Paterson A D,Fraser M,et al.A progressive autosomal recessive cataract locus maps to chromosome 9q13-q22.Am J Hum Genet,2001,68:772-777.
[24]Francis PJ,Berry B,Hardcastle AJ,et al.A locus for isolated cataract on human Xp.J Med Genet,2002,39:105-109.
[25]何守志.晶状体病学.北京:人民卫生出版社,2004:27-30.
[26]李妮,刘谊.常染色体显性先天性白内障的基因定位与克隆.眼科研究,2005,23(1):100-103.
[27]Wang Jun,Ma Xu,Gu Feng,et al.A missense mutation S228P in the CRYBB1gene causes autosomal dominant congenital cataract.Chin Med J,2007,120(9):820.
[28]Santhiya ST,Shyam Manohar M,Rawlley D,et al.Novel mutations in the gamma-crystallin gene cause autosomal dominant congenital cataracts.J Med Genet,2002,39(5):352-8.
[29]汤霞靖,姚克.晶体蛋白基因与先天性白内障.国外医学眼科学分册,2004,28(6):374-377。
[30]齐艳华,贾红艳,黄尚志等.晶体蛋白βA1基因缺失突变导致常染色体显性遗传核性先天性白内障.中华医学遗传学杂志,2003,20(6):486-489。
[31]齐艳华,马兰茗.晶体蛋白βB2基因突变导致常染色体显性遗传先天性白内障.眼科新进展,2008,28(9):676-876。
[32]Lu S,Zhao C,Jiao H,et al.Two Chinese families with pulverulent congenital cataracts and delta G91 CRYBA1 mutations.Mol Vis,2007,13:1154-1160.
[33]Wang J,Ma X,Gu F,et al.A missense mutation S228P in the CRYBB1 gene causes autosomal dominant congenital cataract.Chin Med J(Engl),2007,120(9):820-824.
[34]Liu M,Ke T,Wang Z,et al.Identification of a CRYAB mutation associated with autosomal dominant posterior polar cataract in a Chinese family.Invest Ophthalmol Vis Sci,2006,47(8):3461-3466.
[35]Cobb BA,Petrash JM.Structural and functional changes in the alpha-A-crystallin R116C mutant in hereditary cataracts.Biochemistry,2000,39:15791-15798.
[36]Berry V,Francis P,Reddy MA.Alpha-B crystallin gene(CRYAB) mutation causes dominant congenital posterior polar cataract in humans.Am J Hum Genet,2001,69:1141-1145.
[37]Santhiya ST,Soker T,Klopp N,et al.Identification of a novel,putative cataract-causing allele in CRYAA(G98R)in an Indian family.Mol Vis,2006,12:768-773.
[38]Berry V,Francis P,Reddy MA,et al.Alpha-B crystallin gene(CRYAB)mutation causes dominant congenital posterior polar cataract in humans.Am J Hum Genet.2001,69(5):1141-1145.
[39]Qi Y,Jia H,Huang S,et al.A deletion mutation in the betaA1/A3 crystallin gene(CRYBA1/A3)is associated with autosomal dominant congenital nuclear cataract in a Chinese family.Hum Genet,2004,114(2):192-197.
[40]Santhiya ST,Manisastry SM,Rawlley D,et al.Mutation analysis of congenital cataracts in Indian families:identification of SNPS and a new causative allele in CRYBB2 gene.Invest Ophthalmol Vis Sci,2004,45(10):3599-3607.
[41]Willoughby CE,Shafiq A,Ferrini W,et al.CRYBB1 mutation associated with congenital cataract and microcomea.Mol Vis,2005,11:587-593.
[42]Xu WZ,Zheng S,Xu SJ,et al.Autosomal dominant coralliform cataract related to a missense mutation of the gamma D-crystallin gene.Chin Med J(Engl),2004,117(5):727-732.
[43]Gonzalez Huerta LM,Messina Baas OM,Cuevas Covarrubias SA.A family with autosomal dominant primary congenital cataract associated with a CRYGC mutation:evidence of clinical heterogeneity.Mol Vis,2007,13:1333-1338.
[44]Sun H,Ma Z,Li Y,et al.Gamma-S crystallin gene(CRYGS)mutation Causes dominant progressive cortical cataract in humans.J Med Genet,2005,42(9):706-710.
[45]林辉,王丽,周南,等.晶状体膜蛋白MIP基因C末端一个新的错义突变导致双眼多形性先天性白内障.中华医学遗传学杂志,2008,25(1):6-10。
[46]林婴,刘妮妮,雷春涛,等.一个先天性白内障家系缝隙连接蛋白基因新突变.中华医学遗传学杂志,2008,25(1):59-62。
[47]林英,郑建秋,刘平.先天性白内障与缝隙连接蛋白Cx50.国际眼科杂志,2007,7(6):1658-1661。
[48]Guleria K,Sperling K,Singh D,et al.A novel mutation in the connexin 46(GJA3)gene associated with autosomal dominant congenital cataract in an Indian family.Mol Vis,2007,13:1657-1665.
[49]Vanita V,Hennies HC,Singh D,et al.A novel mutation in GJA8 associated with autosomal dominant congenital cataract in a family of Indian origin.Mol Vis,2006,12:1217-1222.
[50]Gu F,Zhai H,Li D,et al.A hovel mutation in major intrinsic protein of the Iens gene(MIP)underlies autosomal dominant cataract in a Chinese family.Mol Vis,2007,13:1651-1656.
[51]夏欣一,杨滨,崔英霞,等。常染色体显性先天性白内障致病基因研究进展。中国优生与遗传杂志.2008,16(6):10-12。
[52]Semina EV,Ferrell RE,Mintz-Hittner HA.A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD.Nature Genet,1998,19:167-170
[53]Addison PK,Berry V,Ionides AC.Posterior polar cataract is the predominant consequence of a recurrent mutation in the PITX3 gene.Br J Ophthalmol,2005,89(2):138-141.
[54]Jordan T,Hanson I,Zaletayev D.The human PAX6 gene is mutated in two patients with aniridia.Nature Genet,1992,1:328-332.
[55]Burdon KP,McKay JD,Wirth MG,et al.The PITX3 gene in posterior polar congenital cataract in Australia.Mol Vis,2006,12:367-371.
[56]葛坚.眼科学.北京:人民卫生出版社,2005:219-221.
[57]曹志红,李杨.转录调节因子基因突变与先天性白内障.国际眼科纵览,2007,31(2):92-95.
[58]Ke T,Wang QK,Ji B,et al.Novel HSF4 mutation causes congenital total white cataract in a Chinese family.Am J Ophthalmol,2006,142(2):298-303.
[59]Perveen R,Favor J,Jamieson RV,et al.A heterozygous c-Maf transactivation domain mutation causes congenital cataractand enhances target gene activation.Htim Mol Genet,2007,16(9):1030-1038.
[60]Vanita V Singh D,Robinson PN,Sperling K,et al.A novel mutation in the DNA-binding domain of MAF at 16q23.1 associated with autosomal dominant “cerulean cataract” in an Indian family.Am J Med Genet A,2006,140(6):558-566.
[1]Klein BE,Klein R,Lee KE.Incidence of age-related cataract over a 10-year interval:the Beaver Dam Eye Study.Ophthalmology.2002,109:2052-2057.
[2]H.Bloemendal et al.Ageing and vision:structure,stability and function of lens crystallins.Progress in Biophysics & Molecular Biology 2004,86:407-485.
[3]Sonna LA,Fujita J,Gaffin SL,et al.Invited review:effects of heat and cold stress on mammalian gene expression.J.Appl.Physiol 2002,92:1725-1742.
[4]Csermely P.Chaperone overload is a possible contributor to civilization diseases.Trends Genet.2001,17:701-704.
[5]Magabo KS,Horwitz J,Piatigorsky J,et al.Expression of betaB (2)-crystallin mRNA and protein in retina,brain,and testis.Invest Ophthalmol Vis Sci.2000,41:3056-3060.
[6]Michael R,van Marie J,Vrensen GF,et al.Changes in the refractive index of lens fibre membranes during maturation—impact on lens transparency.Exp Eye Res.2003,77:93-99.
[7]Franceschi C,Valensin S,Bonafe M,et al.The network and the remodeling theories of aging:historical background and new perspectives.Exp.Gerontol.2000,35:879-896.
[8]Kmoch S,Brynda J,Asfaw B,et al.Link between a novel human gammaD-cirystallin allele and a unique cataract phenotype explained by protein crystallography.Hum.Mol.Genet 2000,9:1779-1786.
[9]Patil C,Walter P.Intracellular signaling from the endoplasmic reticulum to the nucleus:the unfolded protein response in yeast and mammals.Cell Biol.2001,13:349-355.
[10]Alizadeh A,Clark JI,Seeberger T,et al.Targeted genomic deletion of the lens-specific intermediate filament protein CP49.Invest.Ophthalmol.Vis.Sci.2002,43:3722-3727.
[11]Michael R,van Marie J,Vrensen GF,et al.Changes in the refractive index of lens fibre membranes during maturation-impact on lens transparency.Exp.Eye Res.2003,77:93-99.
[12]Ueda Y,Duncan MK,David L.Lens proteomics:the accumulation of crystallin modifications in the mouse lens with age.Invest Ophthalmol Vis Sci.2002,43:205-215.
[13]Smith G,Atchison DA,Pierscionek BK.Modeling the power of the aging human eye.J.Opt.Soc.Am.A 1992,9:2111-2117.
[14]Ma ZX,Hanson SRA,Lampi KJ,et al.Age-related changes in human lens crystallins identified by HPLC and mass spectrometry.Exp.Eye.Res 1998,67:21-30.
[15]Bateman,JB,FR yon-Bischhoff,L.Richter,et al.Gene conversion mutation in crystallin,beta-B2 (CRYBB2) in a Chilean family with autosomal dominant cataract.Ophthalmology,2007,114:425-32.
[16]Lampi KJ,Shih M,Ueda Y,et al.Lens proteomics:analysis of rat crystallin sequences and two-dimensional electrophoresis map.Invest.Ophthalmol.Vis.Sci 2002,43:216-224.
[17]Nandrot E,Slingsby C,Basak A,et al.Gamma-D crystallin gene(CRYGD) mutation causes autosomal dominant congenital cerulean cataracts.J Med Genet,2003,40:262-267.
[18]Wistow G,Bernstein SL,Wyatt MK,et al.Expressed sequence tag analysis of adult human lens for the NEIBank Project:over 2000 non-redundant transcripts,novel genes and splice variants.Mol.Vis 2002,8:171-184.
[19]Shen T X,Yao K,Xu W,et al.Special fasciculiform caused by a mutuation in the y-D crystallin gene.Mol.Vis 2004,10:233-239.
[20]Nijveen H,Civil A,Van Genesen ST,et al.Regulatory elements in the rat beta B2-crystallin promoter.Exp.Eye Res.2001,73:703-710.
[21]Thomas L Jen,Christian S,Uwe Schroer et al.Elongation of Axons during Regeneration Involves Retinal Crystallin |3b2 (crybb2).Molecular & Cellular Proteomics.2007,6:895-907.
[22]Kevin M.DuPrey,Kimberly M.Robinson,et al.Subfertility in mice harboring a mutation in PB2-crystallin.Molecular Vision,2007,13:366-373.