Disease relevance of Xpr1

• These data, together with genetic mapping of the mink cell focus-forming virus cell surface receptor locus to this same region of chromosome 1, suggest that Sxv may encode a wild mouse variant of the mink cell focus-forming virus receptor that allows penetration by xenotropic murine leukemia viruses [1].
• Rmc1, the cellular receptor for the polytropic class of murine retroviruses, determines the tissue tropism of the virus and therefore plays a critical role in the pathogenesis of polytropic virus-induced leukemia [2].
• The rate of MCF virus spread through a population of permissive human cells was increased by establishment of trans activation, indicating that Syg1 receptor-dependent and -independent pathways function in parallel [3].
• These findings suggest that PDGF plays a crucial role in the pathogenesis of pulmonary fibrosis, and that XR gene transfer using the HVJ-liposome method may limit the progression of pulmonary fibrosis [4].

High impact information on Xpr1

• Susceptibility to infection by polytropic/MCF and also by closely related xenotropic MLV has been mapped to Rmc1 on mouse chromosome 1 (refs 5-7) [5].
• From hamster cell clones identified in the screen, we recovered a mouse cDNA that maps to Rmc1 and confers MCF MLV infection when expressed in nonpermissive cell lines [5].
• It encodes a membrane protein related to Syg1p (suppressor of yeast G alpha deletion; ref. 8). The receptor-binding domain of the MCF MLV envelope protein binds specifically to Xenopus laevis oocytes that express mouse Syg1, suggesting it functions as a receptor that mediates virus entry [5].
• When added to fibroblast cultures the soluble XR protein blocked the ability of BB-PDGF to stimulate DNA synthesis but did not alter the mitogenic effect of AA-PDGF [6].
• In the presence of ligand the soluble XR protein formed complexes that migrated on sodium dodecyl sulfate gels at the size expected for dimers of the protein [6].

Biological context of Xpr1

• Instead, susceptibility is controlled by a single dominant gene, designated Sxv, which maps to chromosome 1 [1].
• In this report we describe the refinement of the Rmc1 candidate region to approximately 600 kb and the generation of an integrated somatic cell hybrid, YAC, and bacterial artificial chromosome contig spanning the region [2].
• These hybrids also showed an interesting possibility of preferential reinactivation of the reactivated XR chromosome in the early stages after cell fusion [7].
• To understand the molecular mechanisms underlying extremely high radiosensitivity and rapid apoptosis, we attempted to isolate X-ray-resistant (XR) variants from 3SBH5, a stable subclone of 3SB, by repeating exposure of the cells to 2-5 Gy X-rays [8].
• The regulatory elements mediating the transcriptional effects of the Peroxisome Proliferator Activated Receptor (PPAR)/Retinoid X Receptor heterodimers consist of a direct repeat of a variant of the consensus hexamer AGGTCA with an interspacing of 1 basepair (DR1) [9].

Anatomical context of Xpr1

• An integrated somatic cell hybrid, YAC, and BAC map of the Rmc1 region of mouse chromosome 1 [2].
• Liver X Receptor Agonist T0901317 Inhibition of Glucocorticoid Receptor Expression in Hepatocytes May Contribute to the Amelioration of Diabetic Syndrome in db/db Mice [10].

Associations of Xpr1 with chemical compounds

• Upon amplification of the receptor cDNA sequences by methotrexate a 110-kDa soluble form of the receptor extracellular region (XR) was secreted at 12 mg/liter [6].
• The XR fragment also inhibited the binding of BB-PDGF to PDGFr and the activation of PDGFr tyrosine kinase by BB-PDGF [6].
• The XR gene transfer ameliorated the increases in the wet weight and hydroxyproline content and the histopathologic changes of the lung induced by bleomycin [4].
• DNR, as well as C2-ceramide (5 muM) induced apoptosis in parental 3SBH5 cell, but not in two XR variants, R233 and R316 cells [8].

Other interactions of Xpr1

• Genetic experiments designed to characterize Sxv show that this gene also controls sensitivity to a wild mouse virus with the interference properties of mink cell focus-forming murine leukemia viruses, and that Sxv-mediated susceptibility to xenotropic murine leukemia viruses is restricted by the mink cell focus-forming virus resistance gene Rmcf [1].
• Sxv is closely linked to, but distinct from Bxv-1, the major locus for induction of xenotropic murine leukemia viruses in laboratory mice [1].

Analytical, diagnostic and therapeutic context of Xpr1

• Genetic crosses showed this recessive resistance to be governed by a single gene that maps at or near the gene encoding the polytropic viral receptor, Rmc1 [11].

References