Generation and analysis of Siah2 mutant mice.
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.
Frew
Ian J
IJ
Trescowthick Research Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 3002, Australia.
Hammond
Vicki E
VE
Dickins
Ross A
RA
Quinn
Julian M W
JM
Walkley
Carl R
CR
Sims
Natalie A
NA
Schnall
Ralf
R
Della
Neil G
NG
Holloway
Andrew J
AJ
Digby
Matthew R
MR
Janes
Peter W
PW
Tarlinton
David M
DM
Purton
Louise E
LE
Gillespie
Matthew T
MT
Bowtell
David D L
DD
D000818:Animals; D000831:Animals, Newborn; D000917:Antibody Formation; D005260:Female; D007107:Immune System / Q000254:growth & development; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D008262:Macrophage Activation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D023461:Myeloid Progenitor Cells / Q000166:cytology; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology; D010641:Phenotype; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins
D009687:Nuclear Proteins; D014409:Tumor Necrosis Factor-alpha; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins