Disruption of the murine calpain small subunit gene, Capn4: calpain is essential for embryonic development but not for cell growth and division. 2000

J S Arthur, and J S Elce, and C Hegadorn, and K Williams, and P A Greer
Department of Biochemistry, Department of Pathology, Queen's University, Kingston, Ontario K7L 3N6, Canada.

Calpains are a family of Ca(2+)-dependent intracellular cysteine proteases, including the ubiquitously expressed micro- and m-calpains. Both mu- 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 mu- 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 mu- 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.

UI MeSH Term Description Entries
D002154 Calpain Cysteine proteinase found in many tissues. Hydrolyzes a variety of endogenous proteins including NEUROPEPTIDES; CYTOSKELETAL PROTEINS; proteins from SMOOTH MUSCLE; CARDIAC MUSCLE; liver; platelets; and erythrocytes. Two subclasses having high and low calcium sensitivity are known. Removes Z-discs and M-lines from myofibrils. Activates phosphorylase kinase and cyclic nucleotide-independent protein kinase. This enzyme was formerly listed as EC 3.4.22.4. Calcium-Activated Neutral Protease,Calcium-Dependent Neutral Proteinase,Ca2+-Activated Protease,Calcium-Activated Neutral Proteinase,Calcium-Activated Protease,Calcium-Dependent Neutral Protease,Calpain I,Calpain II,Desminase,Ca2+ Activated Protease,Calcium Activated Neutral Protease,Calcium Activated Neutral Proteinase,Calcium Activated Protease,Calcium Dependent Neutral Protease,Calcium Dependent Neutral Proteinase,Neutral Protease, Calcium-Activated,Neutral Protease, Calcium-Dependent,Neutral Proteinase, Calcium-Activated,Neutral Proteinase, Calcium-Dependent,Protease, Ca2+-Activated,Protease, Calcium-Activated,Protease, Calcium-Activated Neutral,Protease, Calcium-Dependent Neutral,Proteinase, Calcium-Activated Neutral,Proteinase, Calcium-Dependent Neutral
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D005314 Embryonic and Fetal Development Morphological and physiological development of EMBRYOS or FETUSES. Embryo and Fetal Development,Prenatal Programming,Programming, Prenatal
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017353 Gene Deletion A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. Deletion, Gene,Deletions, Gene,Gene Deletions
D051379 Mice The common name for the genus Mus. Mice, House,Mus,Mus musculus,Mice, Laboratory,Mouse,Mouse, House,Mouse, Laboratory,Mouse, Swiss,Mus domesticus,Mus musculus domesticus,Swiss Mice,House Mice,House Mouse,Laboratory Mice,Laboratory Mouse,Mice, Swiss,Swiss Mouse,domesticus, Mus musculus
D018507 Gene Expression Regulation, Developmental Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action during the developmental stages of an organism. Developmental Gene Expression Regulation,Embryologic Gene Expression Regulation,Gene Expression Regulation, Embryologic,Regulation of Gene Expression, Developmental,Regulation of Gene Expression, Embryologic,Regulation, Gene Expression, Developmental,Regulation, Gene Expression, Embryologic

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