title: Targeted disruption of mouse ortholog of the human MYH9 responsible for macrothrombocytopenia with different organ involvement: hematological, nephrological, and otological studies of heterozygous KO mice.
abstract: Among three different isoforms of non-muscle myosin heavy chains (NMMHCs), only NMMHCA is associated with inherited human disease, called MYH9 disorders, characterized by macrothrombocytopenia and characteristic granulocyte inclusions. Here targeted gene disruption was performed to understand fundamental as well as pathological role of the gene for NMMHCA, MYH9. Heterozygous intercrosses yielded no homozygous animals among 552 births, suggesting that MYH9 expression is required for embryonic development. In contrast, MYH9+/- mice were viable and fertile without gross anatomical, hematological, and nephrological abnormalities. Immunofluorescence analysis also showed the normal cytoplasmic distribution of NMMHCA. We further measured the auditory brainstem response and found two of six MYH9+/- mice had hearing losses, whereas the remaining four were comparable to wild-type mice. Such observation may parallel the diverse expression of Alport's manifestations of human individuals with MYH9 disorders and suggest the limited requirement of the gene for maintenance and function of specific organs.
authors.affiliation: Department of Hematology, Nagoya University Graduate School of Medicine, Japan. tmatsu@med.nagoya-u.ac.jp
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsushita
authors.forename: Hideo
authors.initials: H
authors.lastname: Hayashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Kunishima
authors.forename: Mutsuharu
authors.initials: M
authors.lastname: Hayashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Ikejiri
authors.forename: Kyosuke
authors.initials: K
authors.lastname: Takeshita
authors.forename: Yukio
authors.initials: Y
authors.lastname: Yuzawa
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Adachi
authors.forename: Kanji
authors.initials: K
authors.lastname: Hirashima
authors.forename: Michihiko
authors.initials: M
authors.lastname: Sone
authors.forename: Koji
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Takagi
authors.forename: Akira
authors.initials: A
authors.lastname: Katsumi
authors.forename: Kumi
authors.initials: K
authors.lastname: Kawai
authors.forename: Tomoyo
authors.initials: T
authors.lastname: Nezu
authors.forename: Masahide
authors.initials: M
authors.lastname: Takahashi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakashima
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naoe
authors.forename: Tetsuhito
authors.initials: T
authors.lastname: Kojima
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Saito
mesh_terms: D000818:Animals; D001772:Blood Cell Count; D002460:Cell Line; D018390:Gene Targeting / Q000379:methods; D034381:Hearing Loss / Q000175:diagnosis / Q000378:metabolism*; D006801:Humans; D007674:Kidney Diseases / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D020409:Molecular Motor Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D018995:Myosin Heavy Chains / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D009394:Nephritis, Hereditary / Q000378:metabolism / Q000473:pathology; D009928:Organ Specificity; D013329:Structure-Activity Relationship; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000378:metabolism* / Q000473:pathology*; D014018:Tissue Distribution
chemical_list: C103814:MYH9 protein, human; D020409:Molecular Motor Proteins; D018995:Myosin Heavy Chains