Cardiovascular characterization of Pkd2^+/LacZ mice, an animal model for the autosomal dominant polycystic kidney disease type 2 (ADPKD2)

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• 作者：Jö ; rg Stypmann ; Markus A. Engelen ; Stefan Orwat ; Konstantinos Bilbilis ; Markus Rothenburger ; Lars Eckardt ; Wilhelm Haverkamp ; Jü ; rgen Horst ; Bernd Dworniczak ; Petra Pennekamp
• 关键词：Polycystin-2 ; Pkd2 ; APKD ; Cystic kidney disease ; Ultrasound ; Echocardiography
• 刊名：International Journal of Cardiology
• 出版年：2007
• 期刊代码：128_01675273
• 类别：med
• 出版时间：21 August 2007
• 卷：120
• 期：2
• 页码：158-166
• 文件大小：1711 K

摘要

Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in PKD1 or PKD2. Patients with ADPKD have an increased incidence of cardiac valve abnormalities and left ventricular hypertrophy. Systematic analyses of cardiovascular involvement have so far been performed only on genetically unclassified patients or on ADPKD1 patients, but not on genetically defined ADPKD2 patients. Even existing Pkd1 or Pkd2 mouse models were not thoroughly analyzed in this respect. Therefore, the aim of this project was the noninvasive functional cardiovascular characterization of a mouse model for ADPKD2.

Methods

Pkd2^+/LacZ mice and wildtype controls were classified into 8 groups with respect to gender, age and genotype. In addition, two subgroups of female mice were analyzed for cardiac function before and during advanced pregnancy. Doppler-echocardiographic as well as histological studies were performed.

Results

Doppler-echocardiography did not reveal significant cardiovascular changes. Heart rate and left ventricular (LV) length, LV mass, LV enddiastolic and LV endsystolic diameters did not differ significantly among the various groups when comparing wildtype and knockout mice. There were no significant differences except for a tendency towards higher maximal early and late flow velocities over the mitral valve in old wildtype mice.

Conclusions

Non-invasive phenotyping using ultrasound did not reveal significant cardiovascular difference between adult Pkd2^+/LacZ and WT mice. Due to the lack of an obvious renal phenotype in heterozygous mice, it is likely that in conventional ADPKD knock out mouse models severe cardiac problems appear too late to be identified during the reduced lifespan of the animals.