Disruption of the murine calpain small subunit gene, Capn4: calpain is essential for embryonic development but not for cell growth and division

J. Simon C. Arthur, John S. Elce, Carol Hegadorn, Karen Williams, Peter A. Greer

    Research output: Contribution to journalArticle

    268 Citations (Scopus)

    Abstract

    Calpains are a family of Ca2+-dependent intracellular cysteine proteases, including the ubiquitously expressed µ- and m-calpains. Both µ- and m-calpains are heterodimers, consisting of a distinct large 80-kDa catalytic subunit, encoded by the genes Capn1 and Capn2, and a common small 28-kDa regulatory subunit (Capn4). The physiological roles and possible functional distinctions of µ- and m-calpains remain unclear, but suggested functions include participation in cell division and migration, integrin-mediated signal transduction, apoptosis, and regulation of cellular control proteins such as cyclin D1 and p53. Homozygous disruption of murine Capn4 eliminated both µ- and m-calpain activities, but this did not affect survival and proliferation of cultured embryonic stem cells or embryonic fibroblasts, or the early stages of organogenesis. However, mutant embryos died at midgestation and displayed defects in the cardiovascular system, hemorrhaging, and accumulation of erythroid progenitors.

    Original languageEnglish
    Pages (from-to)4474-4481
    Number of pages8
    JournalMolecular and Cellular Biology
    Volume20
    Issue number12
    Publication statusPublished - Jun 2000

    Fingerprint

    Calpain
    Cell Division
    Embryonic Development
    Growth
    Genes
    Cysteine Proteases
    Organogenesis
    Cyclin D1
    Embryonic Stem Cells
    Cardiovascular System
    Integrins
    Cell Movement
    Signal Transduction
    Catalytic Domain
    Embryonic Structures
    Fibroblasts
    Apoptosis
    m-calpain
    Proteins

    Keywords

    • Animals
    • Embryonic and Fetal Development
    • Calpain
    • Mice
    • Gene Expression Regulation, Developmental
    • Gene Deletion
    • Cell Division

    Cite this

    @article{7c6d544f4bd44f7490e673260574ae54,
    title = "Disruption of the murine calpain small subunit gene, Capn4: calpain is essential for embryonic development but not for cell growth and division",
    abstract = "Calpains are a family of Ca2+-dependent intracellular cysteine proteases, including the ubiquitously expressed µ- and m-calpains. Both µ- and m-calpains are heterodimers, consisting of a distinct large 80-kDa catalytic subunit, encoded by the genes Capn1 and Capn2, and a common small 28-kDa regulatory subunit (Capn4). The physiological roles and possible functional distinctions of µ- and m-calpains remain unclear, but suggested functions include participation in cell division and migration, integrin-mediated signal transduction, apoptosis, and regulation of cellular control proteins such as cyclin D1 and p53. Homozygous disruption of murine Capn4 eliminated both µ- and m-calpain activities, but this did not affect survival and proliferation of cultured embryonic stem cells or embryonic fibroblasts, or the early stages of organogenesis. However, mutant embryos died at midgestation and displayed defects in the cardiovascular system, hemorrhaging, and accumulation of erythroid progenitors.",
    keywords = "Animals, Embryonic and Fetal Development, Calpain, Mice, Gene Expression Regulation, Developmental, Gene Deletion, Cell Division",
    author = "Arthur, {J. Simon C.} and Elce, {John S.} and Carol Hegadorn and Karen Williams and Greer, {Peter A.}",
    year = "2000",
    month = "6",
    language = "English",
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    pages = "4474--4481",
    journal = "Molecular and Cellular Biology",
    issn = "0270-7306",
    publisher = "American Society for Microbiology",
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    Disruption of the murine calpain small subunit gene, Capn4 : calpain is essential for embryonic development but not for cell growth and division. / Arthur, J. Simon C.; Elce, John S.; Hegadorn, Carol; Williams, Karen; Greer, Peter A.

    In: Molecular and Cellular Biology, Vol. 20, No. 12, 06.2000, p. 4474-4481.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Disruption of the murine calpain small subunit gene, Capn4

    T2 - calpain is essential for embryonic development but not for cell growth and division

    AU - Arthur, J. Simon C.

    AU - Elce, John S.

    AU - Hegadorn, Carol

    AU - Williams, Karen

    AU - Greer, Peter A.

    PY - 2000/6

    Y1 - 2000/6

    N2 - Calpains are a family of Ca2+-dependent intracellular cysteine proteases, including the ubiquitously expressed µ- and m-calpains. Both µ- and m-calpains are heterodimers, consisting of a distinct large 80-kDa catalytic subunit, encoded by the genes Capn1 and Capn2, and a common small 28-kDa regulatory subunit (Capn4). The physiological roles and possible functional distinctions of µ- and m-calpains remain unclear, but suggested functions include participation in cell division and migration, integrin-mediated signal transduction, apoptosis, and regulation of cellular control proteins such as cyclin D1 and p53. Homozygous disruption of murine Capn4 eliminated both µ- and m-calpain activities, but this did not affect survival and proliferation of cultured embryonic stem cells or embryonic fibroblasts, or the early stages of organogenesis. However, mutant embryos died at midgestation and displayed defects in the cardiovascular system, hemorrhaging, and accumulation of erythroid progenitors.

    AB - Calpains are a family of Ca2+-dependent intracellular cysteine proteases, including the ubiquitously expressed µ- and m-calpains. Both µ- and m-calpains are heterodimers, consisting of a distinct large 80-kDa catalytic subunit, encoded by the genes Capn1 and Capn2, and a common small 28-kDa regulatory subunit (Capn4). The physiological roles and possible functional distinctions of µ- and m-calpains remain unclear, but suggested functions include participation in cell division and migration, integrin-mediated signal transduction, apoptosis, and regulation of cellular control proteins such as cyclin D1 and p53. Homozygous disruption of murine Capn4 eliminated both µ- and m-calpain activities, but this did not affect survival and proliferation of cultured embryonic stem cells or embryonic fibroblasts, or the early stages of organogenesis. However, mutant embryos died at midgestation and displayed defects in the cardiovascular system, hemorrhaging, and accumulation of erythroid progenitors.

    KW - Animals

    KW - Embryonic and Fetal Development

    KW - Calpain

    KW - Mice

    KW - Gene Expression Regulation, Developmental

    KW - Gene Deletion

    KW - Cell Division

    M3 - Article

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    VL - 20

    SP - 4474

    EP - 4481

    JO - Molecular and Cellular Biology

    JF - Molecular and Cellular Biology

    SN - 0270-7306

    IS - 12

    ER -