X-inactivation analysis of embryonic lethality in Ocrl wt/−;Inpp5b −/− mice

• DOI: 10.1007/s00335-010-9255-9
• Publication Date: 2010-02-26T07:48:01Z
• Authors: David J. Bernard; Robert L. Nussbaum
• Keywords: Inner cell mass; Trophoblast

Mutations in the human OCRL gene, which encodes a phosphatidylinositol(4,5)bisphosphate 5-phosphatase, result X-linked oculocerebrorenal syndrome of Lowe. Mice with targeted disruption Ocrl have no phenotypic abnormalities. Targeted its closest paralog, Inpp5b, causes male infertility 129S6 background. disruptions both genes are lost utero prior to 9.5-10.5 dpc, indicating that there is functional overlap between two paralogs early development. We analyzed pattern X-inactivation four tissues distinct embryonic origin from wt/−;Inpp5b −/− females explore timing and tissue distribution overlap. was strongly skewed against disrupted − allele being on active X chromosome all tested, selection cell lineages lacking Inpp5b. Extraembryonic also involved lethality because were never any live-born when wt paternal chromosome, preferentially inactivated trophoblast-derived extraembryonic tissues. Live-born found maternal, although fewer numbers than expected. The importance embryos Inpp5b reinforced by successful isolation viable 40,XX −/−;Inpp5b stem inner mass 3.5-dpc blastocyst implantation. These results indicate most lineages, especially