| First Author | Zhang Y | Year | 2012 |
| Journal | Blood | Volume | 119 |
| Issue | 1 | Pages | 238-50 |
| PubMed ID | 21908426 | Mgi Jnum | J:175367 |
| Mgi Id | MGI:5285364 | Doi | 10.1182/blood-2011-06-358853 |
| Citation | Zhang Y, et al. (2012) Mouse models of MYH9-related disease: mutations in nonmuscle myosin II-A. Blood 119(1):238-5 |
| abstractText | We have generated three mouse lines, each with a different mutation in the nonmuscle myosin II-A gene, Myh9 (R702C, D1424N and E1841K). Each line develops MYH9-related disease similar to that found in human patients. R702C mutant human cDNA fused with GFP was introduced into the first coding exon of Myh9, and D1424N and E1841K mutations were introduced directly into the corresponding exons. Homozygous R702C mice die at embryonic day 10.5-11.5 while homozygous D1424N and E1841K mice are viable. All heterozygous and homozygous mutant mice show macrothrombocytopenia with prolonged bleeding times, a defect in clot retraction and increased extramedullary megakaryocytes. Studies of cultured megakaryocytes and live cell imaging of megakaryocytes in the bone marrow show that heterozygous R702C megakaryocytes form fewer and shorter proplatelets with less branching and larger buds. The results indicate that disrupted proplatelet formation contributes to the macrothrombocytopenia in mice and most likely in humans. We also observed premature cataract formation, kidney abnormalities including albuminuria, focal segmental glomerulosclerosis and progressive kidney disease, and mild hearing loss. Our results show that heterozygous mice with mutations in the myosin motor or filament-forming domain manifest similar hematological, eye and kidney phenotypes to humans with MYH9-related diseases. |
