Disease relevance of Inpp5b

• Arabinomannan (AM) oligosaccharides derived from LAM of Mycobacterium tuberculosis H37Rv were isolated and covalently conjugated to tetanus toxoid (TT) or to short-term culture filtrate proteins (antigen 85B (Ag85B) or a 75kDa protein) from M. tuberculosis strain Harlingen [1].

High impact information on Inpp5b

• We created mice deficient in Inpp5b; the mice were viable and fertile without phenotype except for testicular degeneration in males beginning after sexual maturation [2].
• Inpp5b is an ubiquitously expressed type II inositol polyphosphate 5-phosphatase [3].
• In addition, fertilin beta, a sperm surface protein involved in sperm-egg membrane interactions that is normally proteolytically processed during sperm transit through the epididymis, showed reduced levels of processing in the Inpp5b(-/-) animals [3].
• Disrupted sperm function and fertilin beta processing in mice deficient in the inositol polyphosphate 5-phosphatase Inpp5b [3].
• Inpp5b(-/-) mice provide an excellent model to study the role of Sertoli and epididymal epithelial cells in the differentiation and maturation of sperm [3].

Biological context of Inpp5b

• We demonstrate that sperm from Inpp5b(-/-) males have reduced motility and reduced ability to fertilize eggs, although capacitation and acrosome exocytosis appear to be normal [3].
• The position of Inpp5b on mouse Chromosome 4 is in the vicinity of the mouse developmental mutation dysgenetic lens (dyl) [4].
• Our results demonstrate a role for Inpp5b in the regulation of cell adhesion in the testis and in the formation of junctional complexes with neighboring cells, and they emphasize the important and essential role of phosphoinositides in spermatogenesis [5].
• Aberrant gene expression was detected in NT embryos compared with IVF embryos, and MuERV-L and Dnaja2 genes were down-regulated and Inpp5b and Chst12 genes were up-regulated in the NT embryos [6].

Anatomical context of Inpp5b

• Inpp5b was expressed in the Sertoli cells and epididymis and at low levels in the developing germ cells; however, mice lacking Inpp5b in spermatids and not in other cell types generated by conditional gene targeting, were fully fertile [3].
• Here, we demonstrate the accumulation of abnormally swollen, actin-coated, endosome-like structures that contain intact adherens junctions and stain positive for N-cadherin and beta-catenin in the Sertoli cell cytosol of mice deficient in Inpp5b, an inositol polyphosphate 5-phosphatase [5].

Analytical, diagnostic and therapeutic context of Inpp5b

• Using two independent approaches, fluorescence in situ hybridization and interspecific backcross analysis, we show that Inpp5b maps to distal mouse Chromosome 4 [4].

References