Disease relevance of Siah1a

• Osteopenia in Siah1a mutant mice [1].

High impact information on Siah1a

• Siah-1a and Af4 are expressed in Purkinje cells and colocalize in the nucleus of human embryonic kidney 293T and P19 cells [2].
• In contrast to Siah1a knockout mice, which are growth retarded and exhibit defects in spermatogenesis, Siah2 mutant mice are fertile and largely phenotypically normal [3].
• Serum gonadotropin levels are normal in Siah1a mutant mice; however, females are subfertile and males are sterile due to a block in spermatogenesis [4].
• 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 [4].
• The ubiquitin ligase component Siah1a is required for completion of meiosis I in male mice [4].

Biological context of Siah1a

• In this study we identified a striking low bone volume phenotype in these mice (trabecular bone volume was halved compared with wild type mice), linking Siah1a to bone metabolism for the first time [1].
• Markers of bone formation, including osteoblast numbers and osteoid volume, were decreased by up to 40%, whereas the number of osteoclasts was more than doubled in Siah1a mutant mice [1].

Anatomical context of Siah1a

• Although ex vivo osteoblast colony formation was normal in Siah1a mutant mice, mineralization from these cells was elevated in cultures from Siah1a mutant mice, which may explain the reduction in osteoid volume seen in vivo [1].
• However, ex vivo osteoclast formation occurs normally and hematopoietic osteoclast progenitor cell types were present in normal numbers in Siah1a mutant mice [1].
• Moreover, adoptive transfer of Siah1a mutant bone marrow into wild type mice failed to reproduce the osteopenia or increased osteoclast numbers observed in mutant mice [1].

Regulatory relationships of Siah1a

• Siah1a has been implicated in numerous signaling pathways because of its ability to induce ubiquitin-mediated degradation of many protein substrates [1].

Analytical, diagnostic and therapeutic context of Siah1a

• We used gene targeting in mice to analyze the function of Siah1a during mammalian development and reveal novel roles in growth, viability, and fertility [4].

References