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Generation and analysis of Siah2 mutant mice


Frew, IJ; Hammond, VE; Dickins, RA; Quinn, JMW; Walkley, CR; Sims, NA; Schnall, R; Della, NG; Holloway, AJ; Digby, MR; Janes, PW; Tarlinton, DM; Purton, LE; Gillespie, MT; Bowtell, DDL
2003-12
MOLECULAR AND CELLULAR BIOLOGY
Journal Article
23
24
9150-9161
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.
AMER SOC MICROBIOLOGY
TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; INDUCED CELL-DEATH; T-CELL; UBIQUITIN LIGASE; TNF-ALPHA; TRANSCRIPTIONAL REPRESSOR; TARGETED DISRUPTION; MAMMALIAN HOMOLOGS; PROTEASOME PATHWAY
10.1128/MCB.23.24.9150-9161.2003
Refer to copyright notice on published article.

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Creation Date 2003-12-01 12:00:00