Molecular and Cellular Biology, June 2000, p. 4474-4481, Vol. 20, No. 12
Department of
Biochemistry1 and Cancer Research
Laboratories, Department of Pathology,2 Queen's
University, Kingston, Ontario K7L 3N6, Canada
Received 10 August 1999/Returned for modification 28 September
1999/Accepted 16 March 2000
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.
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
Disruption of the Murine Calpain Small Subunit
Gene, Capn4: Calpain Is Essential for Embryonic Development
but Not for Cell Growth and Division

*
Corresponding author. Mailing address: Cancer Research
Laboratories, Department of Pathology, Queen's University, Kingston, Ontario K7L 3N6, Canada. Phone: (613) 533-2813. Fax: (613) 533-6830. E-mail: greerp{at}post.queensu.ca.
Present address: MRC Protein Phosphorylation Unit, University of
Dundee, Dundee DD1 5EH, United Kingdom.
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