Knockout mice are an important tool for human monogenic heart disease studies

被引：5

作者：

Cacheiro, Pilar ^{[1
]}

Spielmann, Nadine ^{[2
]}

Mashhadi, Hamed Haseli ^{[3
]}

Fuchs, Helmut ^{[2
]}

Gailus-Durner, Valerie ^{[2
]}

Smedley, Damian ^{[1
]}

de Angelis, Martin Hrabe ^{[2
,4
,5
]}

机构：

[1] Queen Mary Univ London, William Harvey Res Inst, London EC1M 6BQ, England

[2] Helmholtz Ctr Munich, Inst Expt Genet, German Mouse Clin, D-85764 Munich, Germany

[3] European Mol Biol Lab, European Bioinformat Inst, Hinxton CB10 1SD, England

[4] Tech Univ Munich, Chair Expt Genet, TUM Sch Life Sci, D-85354 Freising Weihenstephan, Germany

[5] German Ctr Diabet Res DZD, D-85764 Neuherberg, Germany

来源：

DISEASE MODELS & MECHANISMS | 2022年 / 16卷 / 05期

基金：

美国国家卫生研究院;

关键词：

Knockout mice; Monogenic heart disease; Multisystemic phenotypes; MOUSE; DISORDERS; PERSPECTIVES; CONSORTIUM; SCREENS;

D O I：

10.1242/dmm.049770

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Mouse models are relevant to studying the functionality of genes involved in human diseases; however, translation of phenotypes can be challenging. Here, we investigated genes related to monogenic forms of cardiovascular disease based on the Genomics England PanelApp and aligned them to International Mouse Phenotyping Consortium (IMPC) data. We found 153 genes associated with cardiomyopathy, cardiac arrhythmias or congenital heart disease in humans, of which 151 have one-to-one mouse orthologues. For 37.7% (57/151), viability and heart data captured by electrocardiography, transthoracic echocardiography, morphology and pathology from embryos and young adult mice are available. In knockout mice, 75.4% (43/57) of these genes showed non-viable phenotypes, whereas records of prenatal, neonatal or infant death in humans were found for 35.1% (20/57). Multisystem phenotypes are common, with 58.8% (20/34) of heterozygous (homozygous lethal) and 78.6% (11/14) of homozygous (viable) mice showing cardiovascular, metabolic/homeostasis, musculoskeletal, hematopoietic, nervous system and/or growth abnormalities mimicking the clinical manifestations observed in patients. These IMPC data are critical beyond cardiac diagnostics given their multisystemic nature, allowing detection of abnormalities across physiological systems and providing a valuable resource to understand pleiotropic effects.

引用

页数：10

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