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

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

C2 - 10825211

SN - 0270-7306

VL - 20

SP - 4474

EP - 4481

JO - Molecular and Cellular Biology

JF - Molecular and Cellular Biology

IS - 12

ER -