Generation and characterization of mice with Myh9 deficiency.
Mutant alleles of MYH9 encoding a class II non-muscle myosin heavy chain-A (NMMHC-IIA) have been linked to hereditary megathrombocytopenia with or without additional clinical features that include sensorineural deafness, cataracts, and nephritis. To assess its biological role in the affected targets, particularly the inner ear, we have generated and characterized mice with Myh9 deficiency. These mice were generated using the XA136 ES cell line (BayGenomics, http://baygenomics.ucsf.edu/) carrying gene trap insertion in Myh9, within the intron flanking exons 4 and 5. Mice heterozygous for the Myh9 null allele, Myh9 +/- were expanded on C57BL/6J background. Intercross of the Myh9 +/- mice did not yield Myh9 -/- pups, indicating embryonic lethality, subsequently determined to occur at or before E7.5, thus precluding a post-natal analysis of the effects of complete Myh9 deficiency. The heterozygous mice were normal for their hearing, parameters of platelet integrity and renal function despite their Myh9 haplo-insufficiency. In addition, the age-dependent auditory threshold of the Myh9 +/- mice and their wild type littermates, spanning from 3 to 12 months of age, were similar indicating that Myh9 haplo-insufficiency does not contribute towards accelerated age-related hearing loss (AHL). The embryonic lethality associated with the complete Myh9 deficiency establishes a critical role for this non-muscle myosin in fetal development. The results of these studies do not support the Myh9 haploinsufficiency as a pathogenic factor in the etiology of auditory dysfunction.
Mhatre
Anand N
AN
Laboratory of Molecular Genetics, Department of Otolaryngology, New York University School of Medicine, 560 First Ave, TCH 513, New York, NY 10016, USA. a.mhatre@med.nyu.edu
Li
Yan
Y
Bhatia
Nitin
N
Wang
Kevin H
KH
Atkin
Graham
G
Lalwani
Anil K
AK
D000818:Animals; D003433:Crosses, Genetic; D004195:Disease Models, Animal; D007758:Ear, Inner / Q000378:metabolism* / Q000503:physiopathology; D047108:Embryonic Development; D020022:Genetic Predisposition to Disease; D034381:Hearing Loss / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006579:Heterozygote; D051379:Mice; D008822:Mice, Transgenic; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics*; D024507:Nonmuscle Myosin Type IIA / Q000096:biosynthesis / Q000235:genetics*; D009928:Organ Specificity
C525088:Myh9 protein, mouse; D024507:Nonmuscle Myosin Type IIA; D018995:Myosin Heavy Chains