牛肌肉生长抑制素基因突变的遗传效应与育种应用
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摘要
肌肉生长抑制素(myostatin,MSTN)基因主要在骨骼肌中表达,参与调控骨骼肌的生长发育。MSTN基因在不同物种中具有极强的进化保守性,同时还具有较多的突变多态性。在牛的不同品种中,存在不同位点的有义突变,突变型牛均表现为骨骼肌发达,呈现双肌表型,生长速度与产肉率显著提高。同时,该基因突变也引起显著的生理性遗传效应。对国内外肉牛的MSTN基因突变类型、突变后遗传效应及在肉牛育种应用等方面作了重点阐述,以期为我国地方品种肉牛改良和选育研究提供参考。
The myostatin( MSTN) gene mainly expresses and participates in the regulation of skeletal muscle growth and development. The MSTN gene not only has strong evolutionary conservation,but also has more mutation polymorphisms. In several cattle breeding,kinds of sense mutations at different location of the MSTN have been clarified. All of the sense MSTN mutations resulted in hypertrophic skeletal muscles,which the mutant cattle have the double muscle phenotype,and increase the growth and meat yield. Simultaneously,some of the mutant cattle arise varieties of negative effects. This review focused on the mutation types of MSTN gene,the mutated genetic effects as well as the possible application in beef cattle breeding. The paper would provide data for the research on improvement and breeding of local beef cattle in China.
The myostatin( MSTN) gene mainly expresses and participates in the regulation of skeletal muscle growth and development. The MSTN gene not only has strong evolutionary conservation,but also has more mutation polymorphisms. In several cattle breeding,kinds of sense mutations at different location of the MSTN have been clarified. All of the sense MSTN mutations resulted in hypertrophic skeletal muscles,which the mutant cattle have the double muscle phenotype,and increase the growth and meat yield. Simultaneously,some of the mutant cattle arise varieties of negative effects. This review focused on the mutation types of MSTN gene,the mutated genetic effects as well as the possible application in beef cattle breeding. The paper would provide data for the research on improvement and breeding of local beef cattle in China.
引文
[1]Lee S J,Mc Pherron A C.Regulation of myostatin activity and muscle growth[J].Proc.Natl.Acad.Sci.USA,2001,98:9306-9311.
[2]Fernandez C,Barroso A,Canon J,et al..Myostatin dominant negative allele products interact positively with wild type monomers[J].Anim.Biotechnol.,2004,15:133-143.
[3]Bellinge R H,Liberles D A,Iaschi S P,et al..Myostatin and its implications on animal breeding:A review[J].Anim.Genet.,2005,36:1-6.
[4]刘博,韩志国,高腾云.牛双肌基因遗传机制及研究进展[J].中国农学通报,2011,27:333-336.
[5]Mc Pherron A C,Lee S J.Double muscling in cattle due to mutations in the myostatin gene[J].Proc.Natl.Acad.Sci.USA,1997,94:12457-12461.
[6]Charlier C,Coppieters W,Farnir F,et al..The mh gene causing double-muscling in cattle maps to bovine Chromosome 2[J].Mamm.Genome,1995,6:788-792.
[7]Grobet L,Martin L J,Poncelet D,et al..A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle[J].Nat.Genet.,1997,17:71-74.
[8]Fiems L O.Double muscling in cattle:Genes,husbandry,carcasses and meat[J].Animals(Basel),2012,2:472-506.
[9]Szabo G,Dallmann G,Muller G,et al..A deletion in the myostatin gene causes the compact(Cmpt)hypermuscular mutation in mice[J].Mamm.Genome,1998,9:671-672.
[10]Clop A,Marcq F,Takeda H,et al..A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep[J].Nat.Genet.,2006,38:813-818.
[11]Mosher D S,Quignon P,Bustamante C D,et al..A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs[J].PLo S Genet.,2007,3:e79.
[12]Schuelke M,Wagner K R,Stolz L E,et al..Myostatin mutation associated with gross muscle hypertrophy in a child[J].N.Engl.J.Med.,2004,350:2682-2688.
[13]Kambadur R,Sharma M,Smith T P,et al..Mutations in myostatin(GDF8)in double-muscled Belgian blue and Piedmontese cattle[J].Genome Res.,1997,7:910-916.
[14]Phocas F.Genetic analysis of breeding traits in a Charolais cattle population segregating an inactive myostatin allele[J].J.Anim.Sci.,2009,87:1865-1871.
[15]Esmailizadeh A K,Bottema C D,Sellick G S,et al..Effects of the myostatin F94L substitution on beef traits[J].J.Anim.Sci.,2008,86:1038-1046.
[16]Bouyer C,Forestier L,Renand G,et al..Deep intronic mutation and pseudo exon activation as a novel muscular hypertrophy modifier in cattle[J].PLo S ONE,2014,9:e97399.
[17]Dierks C,Eder J,Glatzer S,et al..A novel myostatin mutation in double-muscled German Gelbvieh[J].Anim.Genet.,2015,46:91-92.
[18]Grobet L,Poncelet D,Royo L J,et al..Molecular definition of an allelic series of mutations disrupting the myostatin function and causing double-muscling in cattle[J].Mamm.Genome,1998,9:210-213.
[19]史明艳,昝林森,王勇强.秦川牛、南阳牛双肌基因的PCRSSCP检测[J].西北农业学报,2003,12:21-23.
[20]史明艳,昝林森,李保兰,等.牛Myostatin基因单核苷酸多态性分析[J].中国农学通报,2005,21:24-25.
[21]刘桂芬,万发春,宋恩亮,等.渤海黑牛和日本和牛MSTN基因的比较分析[J].家畜生态学报,2009,30:7-9.
[22]刘桂芬,万发春,刘晓牧,等.渤海黑牛MSTN基因多态性位点与体尺性状的关联性分析[J].华北农学报,2011,26:17-21.
[23]郭丹,曹阳,张嘉保,等.草原红牛MSTN基因第一外显子SNPs多态性分析[J].现代畜牧兽医,2007,11:12-14.
[24]张胜,张永宏,高妍,等.草原红牛肌生成抑制素基因内含子1多态性及部分屠宰性状的相关性分析[J].中国兽医学报,2010,30:1557-1560.
[25]刘洪瑜,杨漫漫,姬云涛,等.4个牛群体MSTN基因第1外显子单核苷酸多态性分析[J].安徽农业大学学报,201441:380-384.
[26]和占星,亐开兴,张继才,等.BMY牛MSTN基因exon 2克隆及序列分析[J].中国牛业科学,2013,39:1-5.
[27]王娇娇,张世伟,张丽君,等.辽育白牛MSTN基因分子克隆及序列分析[J].现代畜牧兽医,2016(10):21-27.
[28]张沅.中国畜禽遗传资源志:猪志[M].北京:中国农业出版社,2011.
[29]孙少华,李雪梅,魏学蕊,等.牛肌肉生长抑制素(MSTN)基因的检测、分型研究[J].中国农业科技导报,2001,3:66-67.
[30]梁春年,丁学智,包鹏甲,等.牦牛MSTN基因分子克隆及序列分析[J].华北农学报,2013,28:76-81.
[31]刘应祥,王海芳,闫永红,等.牦牛MSTN基因第2外显子的遗传变异分析[J].甘肃农业大学学报,2015(5):15-19.
[32]张丽,刘丽霞,李强子,等.天祝白牦牛MSTN基因编码区克隆及生物信息学分析[J].浙江农业学报,2017,29:618-624.
[33]常春芳,冀德君,常洪,等.中国4个牛种MSTN基因外显子2多态性分析与其系统发生关系研究[J].安徽农业科学,2008,36:5790-5791.
[34]冀德君,常洪,常春芳,等.中国牛属4个物种MSTN基因的遗传变异研究[J].畜牧兽医学报,2008,39:701-704.
[35]Wegner J,Albrecht E,Fiedler I,et al..Growth-and breed-related changes of muscle fiber characteristics in cattle[J].J.Anim.Sci.,2000,78:1485-1496.
[36]Albrecht E,Teuscher F,Ender K,et al..Growth-and breedrelated changes of muscle bundle structure in cattle[J].J.Anim.Sci.,2006,84:2959-2964.
[37]Albrecht E,Lembcke C,Wegner J,et al..Prenatal muscle fiber development and bundle structure in beef and dairy cattle[J].J.Anim.Sci.,2013,91:3666-3673.
[38]Girgenrath S,Song K,Whittemore L A.Loss of myostatin expression alters fiber-type distribution and expression of myosin heavy chain isoforms in slow-and fast-type skeletal muscle[J].Muscle Nerve,2005,31:34-40.
[39]Picard B,Lefaucheur L,Berri C,et al..Muscle fibre ontogenesis in farm animal species[J].Reprod.Nutr.Dev.,2002,42:415-431.
[40]Arthur P F,Makarechian M,Price M A,et al..Heterosis,maternal and direct effects in double-muscled and normal cattle:I.Reproduction and growth traits[J].J.Anim.Sci.,1989,67:902-910.
[41]Pilarczyk R,Wojcik J.Comparison of body weight and reproduction performance in cows of various beef breeds managed under equal conditions in West Pomerania[J].Archiv.Fur.Tierzucht.,2008,51:318-328.
[42]Piedrafita J,Quintanilla R,Sa1udo C,et al..Carcass quality of 10 beef cattle breeds of the Southwest of Europe in their typical production systems[J].Livestock Prod.Sci.,2003,82:1-13.
[43]Cambier C,Clerbaux T,Detry B,et al..Blood oxygen binding in double-muscled calves and dairy calves with conventional muscle conformation[J].Am.J.Veter.Res.,2000,61:299.
[44]Clinquart A,Van Eenaeme C,Mayombo A P,et al..Plasma hormones and metabolites in cattle in relation to breed(Belgian Blue vs Holstein)and conformation(double-muscled vs dualpurpose type)[J].Vet.Res.Commun.,1995,19:185-194.
[45]Fiems L O,Cottyn B G,BoucquéC V,et al..Effect of beef type,body weight and dietary protein content on voluntary feed intake,digestibility,blood and urine metabolites and nitrogen retention[J].J.Anim.Physiol.Anim.Nutr.,1997,77:1-9.
[46]Arthur P F.Double muscling in cattle:A review[J].Austr.J.Agric.Res.,1995,46:1493-1515.
[47]Casas E,Keele J W,Shackelford S D,et al..Association of the muscle hypertrophy locus with carcass traits in beef cattle[J].J.Anim.Sci.,1998,76:468-473.
[48]Casas E,Keele J W,Fahrenkrug S C,et al..Quantitative analysis of birth,weaning,and yearling weights and calving difficulty in Piedmontese crossbreds segregating an inactive myostatin allele[J].J.Anim.Sci.,1999,77:1686.
[49]Short R E,Macneil M D,Grosz M D,et al..Pleiotropic effects in Hereford,Limousin,and Piedmontese F2crossbred calves of genes controlling muscularity including the Piedmontese myostatin allele[J].J.Anim.Sci.,2002,80:1-11.
[50]Sellick G S,Pitchford W S,Morris C A,et al..Effect of myostatin F94L on carcass yield in cattle[J].Anim.Genet.,2007,38:440-446.
[51]Wheeler T L,Cundiff L V,Shackelford S D,et al..Characterization of biological types of cattle(Cycle V):Carcass traits and longissimus palatability[J].J.Anim.Sci.,2001,79:1209-1222.
[52]Wiener P,Smith J A,Lewis A M,et al..Muscle-related traits in cattle:The role of the myostatin gene in the South Devon breed[J].Genet.Select.Evol.Gse,2002,34:1-12.
[53]Allais S,Leveziel H,Hocquette J F,et al..Fine mapping of quantitative trait loci underlying sensory meat quality traits in three French beef cattle breeds[J].J.Anim.Sci.,2014,92:4329-4341.
[54]Ramayo-Caldas Y,Renand G,Ballester M,et al..Multi-breed and multi-trait co-association analysis of meat tenderness and other meat quality traits in three French beef cattle breeds[J].Genet.Sel.Evol.,2016,48:37.
[55]Luo J,Song Z,Yu S,et al..Efficient generation of Myostatin(MSTN)biallelic mutations in cattle using Zinc finger nucleases[J].PLo S ONE,2014,9:e95225.
[56]Cai C,Qian L,Jiang S,et al..Loss-of-function myostatin mutation increases insulin sensitivity and browning of white fat in Meishan pigs[J].Oncotarget,2017,8:34911-34922.
[57]Jiang Y L,Li N,Du L X,et al..Relationship of T→A mutation in the promoter region of myostatin gene with growth traits in swine[J].J.Genet.Genom.,2002,29:413-416.
[58]Qian L,Tang M,Yang J,et al..Targeted mutations in myostatin by zinc-finger nucleases result in double-muscled phenotype in Meishan pigs[J].Sci.Rep.,2015,5:14435.
[59]Dunner S,Miranda M E,Amigues Y,et al..Haplotype diversity of the myostatin gene among beef cattle breeds[J].Genet.Sel.Evol.,2003,35:103-118.
[2]Fernandez C,Barroso A,Canon J,et al..Myostatin dominant negative allele products interact positively with wild type monomers[J].Anim.Biotechnol.,2004,15:133-143.
[3]Bellinge R H,Liberles D A,Iaschi S P,et al..Myostatin and its implications on animal breeding:A review[J].Anim.Genet.,2005,36:1-6.
[4]刘博,韩志国,高腾云.牛双肌基因遗传机制及研究进展[J].中国农学通报,2011,27:333-336.
[5]Mc Pherron A C,Lee S J.Double muscling in cattle due to mutations in the myostatin gene[J].Proc.Natl.Acad.Sci.USA,1997,94:12457-12461.
[6]Charlier C,Coppieters W,Farnir F,et al..The mh gene causing double-muscling in cattle maps to bovine Chromosome 2[J].Mamm.Genome,1995,6:788-792.
[7]Grobet L,Martin L J,Poncelet D,et al..A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle[J].Nat.Genet.,1997,17:71-74.
[8]Fiems L O.Double muscling in cattle:Genes,husbandry,carcasses and meat[J].Animals(Basel),2012,2:472-506.
[9]Szabo G,Dallmann G,Muller G,et al..A deletion in the myostatin gene causes the compact(Cmpt)hypermuscular mutation in mice[J].Mamm.Genome,1998,9:671-672.
[10]Clop A,Marcq F,Takeda H,et al..A mutation creating a potential illegitimate microRNA target site in the myostatin gene affects muscularity in sheep[J].Nat.Genet.,2006,38:813-818.
[11]Mosher D S,Quignon P,Bustamante C D,et al..A mutation in the myostatin gene increases muscle mass and enhances racing performance in heterozygote dogs[J].PLo S Genet.,2007,3:e79.
[12]Schuelke M,Wagner K R,Stolz L E,et al..Myostatin mutation associated with gross muscle hypertrophy in a child[J].N.Engl.J.Med.,2004,350:2682-2688.
[13]Kambadur R,Sharma M,Smith T P,et al..Mutations in myostatin(GDF8)in double-muscled Belgian blue and Piedmontese cattle[J].Genome Res.,1997,7:910-916.
[14]Phocas F.Genetic analysis of breeding traits in a Charolais cattle population segregating an inactive myostatin allele[J].J.Anim.Sci.,2009,87:1865-1871.
[15]Esmailizadeh A K,Bottema C D,Sellick G S,et al..Effects of the myostatin F94L substitution on beef traits[J].J.Anim.Sci.,2008,86:1038-1046.
[16]Bouyer C,Forestier L,Renand G,et al..Deep intronic mutation and pseudo exon activation as a novel muscular hypertrophy modifier in cattle[J].PLo S ONE,2014,9:e97399.
[17]Dierks C,Eder J,Glatzer S,et al..A novel myostatin mutation in double-muscled German Gelbvieh[J].Anim.Genet.,2015,46:91-92.
[18]Grobet L,Poncelet D,Royo L J,et al..Molecular definition of an allelic series of mutations disrupting the myostatin function and causing double-muscling in cattle[J].Mamm.Genome,1998,9:210-213.
[19]史明艳,昝林森,王勇强.秦川牛、南阳牛双肌基因的PCRSSCP检测[J].西北农业学报,2003,12:21-23.
[20]史明艳,昝林森,李保兰,等.牛Myostatin基因单核苷酸多态性分析[J].中国农学通报,2005,21:24-25.
[21]刘桂芬,万发春,宋恩亮,等.渤海黑牛和日本和牛MSTN基因的比较分析[J].家畜生态学报,2009,30:7-9.
[22]刘桂芬,万发春,刘晓牧,等.渤海黑牛MSTN基因多态性位点与体尺性状的关联性分析[J].华北农学报,2011,26:17-21.
[23]郭丹,曹阳,张嘉保,等.草原红牛MSTN基因第一外显子SNPs多态性分析[J].现代畜牧兽医,2007,11:12-14.
[24]张胜,张永宏,高妍,等.草原红牛肌生成抑制素基因内含子1多态性及部分屠宰性状的相关性分析[J].中国兽医学报,2010,30:1557-1560.
[25]刘洪瑜,杨漫漫,姬云涛,等.4个牛群体MSTN基因第1外显子单核苷酸多态性分析[J].安徽农业大学学报,201441:380-384.
[26]和占星,亐开兴,张继才,等.BMY牛MSTN基因exon 2克隆及序列分析[J].中国牛业科学,2013,39:1-5.
[27]王娇娇,张世伟,张丽君,等.辽育白牛MSTN基因分子克隆及序列分析[J].现代畜牧兽医,2016(10):21-27.
[28]张沅.中国畜禽遗传资源志:猪志[M].北京:中国农业出版社,2011.
[29]孙少华,李雪梅,魏学蕊,等.牛肌肉生长抑制素(MSTN)基因的检测、分型研究[J].中国农业科技导报,2001,3:66-67.
[30]梁春年,丁学智,包鹏甲,等.牦牛MSTN基因分子克隆及序列分析[J].华北农学报,2013,28:76-81.
[31]刘应祥,王海芳,闫永红,等.牦牛MSTN基因第2外显子的遗传变异分析[J].甘肃农业大学学报,2015(5):15-19.
[32]张丽,刘丽霞,李强子,等.天祝白牦牛MSTN基因编码区克隆及生物信息学分析[J].浙江农业学报,2017,29:618-624.
[33]常春芳,冀德君,常洪,等.中国4个牛种MSTN基因外显子2多态性分析与其系统发生关系研究[J].安徽农业科学,2008,36:5790-5791.
[34]冀德君,常洪,常春芳,等.中国牛属4个物种MSTN基因的遗传变异研究[J].畜牧兽医学报,2008,39:701-704.
[35]Wegner J,Albrecht E,Fiedler I,et al..Growth-and breed-related changes of muscle fiber characteristics in cattle[J].J.Anim.Sci.,2000,78:1485-1496.
[36]Albrecht E,Teuscher F,Ender K,et al..Growth-and breedrelated changes of muscle bundle structure in cattle[J].J.Anim.Sci.,2006,84:2959-2964.
[37]Albrecht E,Lembcke C,Wegner J,et al..Prenatal muscle fiber development and bundle structure in beef and dairy cattle[J].J.Anim.Sci.,2013,91:3666-3673.
[38]Girgenrath S,Song K,Whittemore L A.Loss of myostatin expression alters fiber-type distribution and expression of myosin heavy chain isoforms in slow-and fast-type skeletal muscle[J].Muscle Nerve,2005,31:34-40.
[39]Picard B,Lefaucheur L,Berri C,et al..Muscle fibre ontogenesis in farm animal species[J].Reprod.Nutr.Dev.,2002,42:415-431.
[40]Arthur P F,Makarechian M,Price M A,et al..Heterosis,maternal and direct effects in double-muscled and normal cattle:I.Reproduction and growth traits[J].J.Anim.Sci.,1989,67:902-910.
[41]Pilarczyk R,Wojcik J.Comparison of body weight and reproduction performance in cows of various beef breeds managed under equal conditions in West Pomerania[J].Archiv.Fur.Tierzucht.,2008,51:318-328.
[42]Piedrafita J,Quintanilla R,Sa1udo C,et al..Carcass quality of 10 beef cattle breeds of the Southwest of Europe in their typical production systems[J].Livestock Prod.Sci.,2003,82:1-13.
[43]Cambier C,Clerbaux T,Detry B,et al..Blood oxygen binding in double-muscled calves and dairy calves with conventional muscle conformation[J].Am.J.Veter.Res.,2000,61:299.
[44]Clinquart A,Van Eenaeme C,Mayombo A P,et al..Plasma hormones and metabolites in cattle in relation to breed(Belgian Blue vs Holstein)and conformation(double-muscled vs dualpurpose type)[J].Vet.Res.Commun.,1995,19:185-194.
[45]Fiems L O,Cottyn B G,BoucquéC V,et al..Effect of beef type,body weight and dietary protein content on voluntary feed intake,digestibility,blood and urine metabolites and nitrogen retention[J].J.Anim.Physiol.Anim.Nutr.,1997,77:1-9.
[46]Arthur P F.Double muscling in cattle:A review[J].Austr.J.Agric.Res.,1995,46:1493-1515.
[47]Casas E,Keele J W,Shackelford S D,et al..Association of the muscle hypertrophy locus with carcass traits in beef cattle[J].J.Anim.Sci.,1998,76:468-473.
[48]Casas E,Keele J W,Fahrenkrug S C,et al..Quantitative analysis of birth,weaning,and yearling weights and calving difficulty in Piedmontese crossbreds segregating an inactive myostatin allele[J].J.Anim.Sci.,1999,77:1686.
[49]Short R E,Macneil M D,Grosz M D,et al..Pleiotropic effects in Hereford,Limousin,and Piedmontese F2crossbred calves of genes controlling muscularity including the Piedmontese myostatin allele[J].J.Anim.Sci.,2002,80:1-11.
[50]Sellick G S,Pitchford W S,Morris C A,et al..Effect of myostatin F94L on carcass yield in cattle[J].Anim.Genet.,2007,38:440-446.
[51]Wheeler T L,Cundiff L V,Shackelford S D,et al..Characterization of biological types of cattle(Cycle V):Carcass traits and longissimus palatability[J].J.Anim.Sci.,2001,79:1209-1222.
[52]Wiener P,Smith J A,Lewis A M,et al..Muscle-related traits in cattle:The role of the myostatin gene in the South Devon breed[J].Genet.Select.Evol.Gse,2002,34:1-12.
[53]Allais S,Leveziel H,Hocquette J F,et al..Fine mapping of quantitative trait loci underlying sensory meat quality traits in three French beef cattle breeds[J].J.Anim.Sci.,2014,92:4329-4341.
[54]Ramayo-Caldas Y,Renand G,Ballester M,et al..Multi-breed and multi-trait co-association analysis of meat tenderness and other meat quality traits in three French beef cattle breeds[J].Genet.Sel.Evol.,2016,48:37.
[55]Luo J,Song Z,Yu S,et al..Efficient generation of Myostatin(MSTN)biallelic mutations in cattle using Zinc finger nucleases[J].PLo S ONE,2014,9:e95225.
[56]Cai C,Qian L,Jiang S,et al..Loss-of-function myostatin mutation increases insulin sensitivity and browning of white fat in Meishan pigs[J].Oncotarget,2017,8:34911-34922.
[57]Jiang Y L,Li N,Du L X,et al..Relationship of T→A mutation in the promoter region of myostatin gene with growth traits in swine[J].J.Genet.Genom.,2002,29:413-416.
[58]Qian L,Tang M,Yang J,et al..Targeted mutations in myostatin by zinc-finger nucleases result in double-muscled phenotype in Meishan pigs[J].Sci.Rep.,2015,5:14435.
[59]Dunner S,Miranda M E,Amigues Y,et al..Haplotype diversity of the myostatin gene among beef cattle breeds[J].Genet.Sel.Evol.,2003,35:103-118.