Recombinant Rat MIS RII Fc Chimera Protein, CF

Müllerian inhibiting substance (MIS), also named anti-Müllerian hormone (AMH) is a tissue-specific TGF-beta superfamily growth factor. Its expression is restricted to fetal testis, plus postnatal testis and ovary (1). MIS induces Mullerian duct (female reproductive tract) regression during sexual differentiation in the male embryo and has been shown to have a regulatory role in gonads postnatally (1). Like other TGF-beta superfamily members, MIS signals via a heteromeric receptor complex consisting of a type I and a type II receptor serine/threonine kinase. Depending on the cell context, different type I receptors (including Act RIA/ALK2, BMP RIA/ALK3, and BMP RIB/ALK6) that are shared by other TGF-beta superfamily members, can be utilized for MIS signaling (1). In contrast, the type II MIS receptor (MIS RII) is unique and does not bind other TGF-beta superfamily members (1, 2). Upon ligand binding, MIS RII recruits the non-ligand binding type I receptor into the complex, resulting in phosphorylation the BMP-like signaling pathway effector proteins Smad1, Smad5 and Smad 8 (1).

The gene for rat MIS RII was isolated separately by two groups working from Sertoli cell and fetal ovary cDNA libraries (3, 4). MIS RII comprises a 557 amino acid (aa) residue type I transmembrane protein with a putative 17 aa signal peptide. Mature MIS RII has a 127 aa cysteine-rich extracellular domain containing 2 potential N-glycosylation sites, a 21 aa transmembrane domain, and a 392 aa cytoplasmic region with a serine/threonine kinase domain (3, 4). Rat MIS RII shares 95% and 82% aa sequence identity with the mouse and human homologues, respectively (5). MIS RII is expressed in the mesenchymal cells surrounding the Mullerian ducts during embryonic development. Postnatally, it is expressed in uterine tissues and rodent Leydig cells, and coexpressed with MIS in the testicular Sertoli and ovarian granulosa cells (1, 6). The expression of MIS RII in the Mullerian mesenchyme is regulated by Wnt7a signaling from nearby epithelium through the canonical Wnt pathway. Wnt7a mutant mice do not express MIS RII, and do not experience Mullerian duct regression (7).