TY - JOUR
T1 - The ubiquitin ligase component Siah1a is required for completion of meiosis I in male mice
AU - Dickins, Ross Alexander
AU - Frew, Ian James
AU - House, Colin M
AU - O'Bryan, Moira Kathleen
AU - Holloway, Andrew J
AU - Haviv, Izhak
AU - Traficante, Nadia
AU - de Kretser, David Morritz
AU - Bowtell, David D L
PY - 2002
Y1 - 2002
N2 - The mammalian Siah genes encode highly conserved proteins containing a RING domain. As components of E3 ubiquitin ligase complexes, Siah proteins facilitate the ubiquitination and degradation of diverse protein partners including -catenin, N-CoR, and DCC. We used gene targeting in mice to analyze the function of Siah1a during mammalian development and reveal novel roles in growth, viability, and fertility. Mutant animals have normal weights at term but are postnatally growth retarded, despite normal levels of pituitary growth hormone. Embryonic fibroblasts isolated from mutant animals grow normally. Most animals die before weaning, and few survive beyond 3 months. Serum gonadotropin levels are normal in Siah1a mutant mice;however, females are subfertile and males are sterile due to a block in spermatogenesis. Although spermatocytesin mutant mice display normal meiotic prophase and meiosis I spindle formation, they accumulate at metaphase to telophase of meiosis I and subsequently undergo apoptosis. The requirement of Siah1a for normal progression beyond metaphase I suggests that Siah1a may be part of a novel E3 complex acting late in the first meiotic division.
AB - The mammalian Siah genes encode highly conserved proteins containing a RING domain. As components of E3 ubiquitin ligase complexes, Siah proteins facilitate the ubiquitination and degradation of diverse protein partners including -catenin, N-CoR, and DCC. We used gene targeting in mice to analyze the function of Siah1a during mammalian development and reveal novel roles in growth, viability, and fertility. Mutant animals have normal weights at term but are postnatally growth retarded, despite normal levels of pituitary growth hormone. Embryonic fibroblasts isolated from mutant animals grow normally. Most animals die before weaning, and few survive beyond 3 months. Serum gonadotropin levels are normal in Siah1a mutant mice;however, females are subfertile and males are sterile due to a block in spermatogenesis. Although spermatocytesin mutant mice display normal meiotic prophase and meiosis I spindle formation, they accumulate at metaphase to telophase of meiosis I and subsequently undergo apoptosis. The requirement of Siah1a for normal progression beyond metaphase I suggests that Siah1a may be part of a novel E3 complex acting late in the first meiotic division.
UR - http://mcb.asm.org.ezproxy.lib.monash.edu.au/content/22/7/2294
UR - http://www.ncbi.nlm.nih.gov/pubmed/11884614
U2 - 10.1128/MCB.22.7.2294-2303.2002
DO - 10.1128/MCB.22.7.2294-2303.2002
M3 - Article
C2 - 11884614
SN - 0270-7306
VL - 22
SP - 2294
EP - 2303
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 7
ER -