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

Tadashi Matsushita, Hideo Hayashi, Shinji Kunishima, Mutsuharu Hayashi, Makoto Ikejiri, Kyosuke Takeshita, Yukio Yuzawa, Tatsuya Adachi, Kanji Hirashima, Michihiko Sone, Koji Yamamoto, Akira Takagi, Akira Katsumi, Kumi Kawai, Tomoyo Nezu, Masahide Takahashi, Tsutomu Nakashima, Tomoki Naoe, Tetsuhito Kojima, Hidehiko Saito

Research output: Contribution to journalArticle

41 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1163-1171
Number of pages9
JournalBiochemical and Biophysical Research Communications
Volume325
Issue number4
DOIs
Publication statusPublished - 24-12-2004
Externally publishedYes

Fingerprint

Genes
Brain Stem Auditory Evoked Potentials
Myosin Heavy Chains
Normal Distribution
Audition
Hearing Loss
Granulocytes
Embryonic Development
Fluorescent Antibody Technique
Protein Isoforms
Animals
Maintenance
Observation
Parturition

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Matsushita, Tadashi ; Hayashi, Hideo ; Kunishima, Shinji ; Hayashi, Mutsuharu ; Ikejiri, Makoto ; Takeshita, Kyosuke ; Yuzawa, Yukio ; Adachi, Tatsuya ; Hirashima, Kanji ; Sone, Michihiko ; Yamamoto, Koji ; Takagi, Akira ; Katsumi, Akira ; Kawai, Kumi ; Nezu, Tomoyo ; Takahashi, Masahide ; Nakashima, Tsutomu ; Naoe, Tomoki ; Kojima, Tetsuhito ; Saito, Hidehiko. / 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. In: Biochemical and Biophysical Research Communications. 2004 ; Vol. 325, No. 4. pp. 1163-1171.
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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.",
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Matsushita, T, Hayashi, H, Kunishima, S, Hayashi, M, Ikejiri, M, Takeshita, K, Yuzawa, Y, Adachi, T, Hirashima, K, Sone, M, Yamamoto, K, Takagi, A, Katsumi, A, Kawai, K, Nezu, T, Takahashi, M, Nakashima, T, Naoe, T, Kojima, T & Saito, H 2004, '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', Biochemical and Biophysical Research Communications, vol. 325, no. 4, pp. 1163-1171. https://doi.org/10.1016/j.bbrc.2004.10.147

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. / Matsushita, Tadashi; Hayashi, Hideo; Kunishima, Shinji; Hayashi, Mutsuharu; Ikejiri, Makoto; Takeshita, Kyosuke; Yuzawa, Yukio; Adachi, Tatsuya; Hirashima, Kanji; Sone, Michihiko; Yamamoto, Koji; Takagi, Akira; Katsumi, Akira; Kawai, Kumi; Nezu, Tomoyo; Takahashi, Masahide; Nakashima, Tsutomu; Naoe, Tomoki; Kojima, Tetsuhito; Saito, Hidehiko.

In: Biochemical and Biophysical Research Communications, Vol. 325, No. 4, 24.12.2004, p. 1163-1171.

Research output: Contribution to journalArticle

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T1 - Targeted disruption of mouse ortholog of the human MYH9 responsible for macrothrombocytopenia with different organ involvement

T2 - Hematological, nephrological, and otological studies of heterozygous KO mice

AU - Matsushita, Tadashi

AU - Hayashi, Hideo

AU - Kunishima, Shinji

AU - Hayashi, Mutsuharu

AU - Ikejiri, Makoto

AU - Takeshita, Kyosuke

AU - Yuzawa, Yukio

AU - Adachi, Tatsuya

AU - Hirashima, Kanji

AU - Sone, Michihiko

AU - Yamamoto, Koji

AU - Takagi, Akira

AU - Katsumi, Akira

AU - Kawai, Kumi

AU - Nezu, Tomoyo

AU - Takahashi, Masahide

AU - Nakashima, Tsutomu

AU - Naoe, Tomoki

AU - Kojima, Tetsuhito

AU - Saito, Hidehiko

PY - 2004/12/24

Y1 - 2004/12/24

N2 - 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.

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