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Molecular and Cellular Biology, June 2000, p. 4474-4481, Vol. 20, No. 12
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

J. Simon C. Arthur,1,dagger John S. Elce,1 Carol Hegadorn,1 Karen Williams,2 and Peter A. Greer1,2,*

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.

* 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.

dagger Present address: MRC Protein Phosphorylation Unit, University of Dundee, Dundee DD1 5EH, United Kingdom.

Molecular and Cellular Biology, June 2000, p. 4474-4481, Vol. 20, No. 12
0270-7306/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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