Generation and analysis of Siah2 mutant mice
Details
Publication Year 2003-12, Volume 23, Issue #24, Page 9150-9161
Journal Title
MOLECULAR AND CELLULAR BIOLOGY
Publication Type
Journal Article
Abstract
Siah proteins function as E3 ubiquitin ligase enzymes to target the degradation of diverse protein substrates. To characterize the physiological roles of Siah2, we have generated and analyzed Siah2 mutant mice. In contrast to Siah1a knockout mice, which are growth retarded and exhibit defects in spermatogenesis, Siah2 mutant mice are fertile and largely phenotypically normal. While previous studies implicate Siah2 in the regulation of TRAF2, Vav1, OBF-1, and DCC, we find that a variety of responses mediated by these proteins are unaffected by loss of Siah2. However, we have identified an expansion of myeloid progenitor cells in the bone marrow of Siah2 mutant mice. Consistent with this, we show that Siah2 mutant bone marrow produces more osteoclasts in vitro than wild-type bone marrow. The observation that combined Siah2 and Siah1a mutation causes embryonic and neonatal lethality demonstrates that the highly homologous Siah proteins have partially overlapping functions in vivo.
Publisher
AMER SOC MICROBIOLOGY
Keywords
TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; INDUCED CELL-DEATH; T-CELL; UBIQUITIN LIGASE; TNF-ALPHA; TRANSCRIPTIONAL REPRESSOR; TARGETED DISRUPTION; MAMMALIAN HOMOLOGS; PROTEASOME PATHWAY
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2003-12-01 12:00:00
Last Modified: 0001-01-01 12:00:00
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