| First Author | Leiter EH | Year | 1998 |
| Journal | MGI Direct Data Submission | Mgi Jnum | J:45281 |
| Mgi Id | MGI:1194727 | Citation | Leiter EH (1998) The Vitamin D Receptor (Vdr) is linked to the Vitamin D Binding Protein/ Group Specific Component (Vdbp/Gc) on Mouse Chr 5. MGI Direct Data Submission |
| abstractText | The mapping of the mouse homolog of the human VDR gene to medial Chromosome 5 extends proximally the region of known homology on this chromosome with human Chromosome 12q [1]. It is noteworthy that the Vdbp/Gc gene encoding the major plasma binding protein for vitamin D and its active 25-dihydroxy metabolites [2] is located within 18 cM of the gene encoding the vitamin D receptor. To more accurately describe the vitamin D binding function of the protein encoded by the Group-specific component locus [2], a nomenclature change from GC to VDBP in humans, and from Gc to Vdbp in mice, has been approved. The mouse locus was initially mapped to mouse Chromosome 5 using a mouse x hamster somatic cell mapping panel [3]. The present report using a segregating backcross DNA panel has more accurately placed this gene on medial Chromosome 5, with no recombinants between this gene and either estrogen sulfotransferase (Ste) or gonadotrophin release hormone receptor (Gnrhr). The 1997 Chromosome 5 Committee Report positions Gnrhr and Ste at 45 cM, and Gc at 51 cM [4]. The present data would suggest that Vdbp (Gc) is considerably closer to the aforementioned loci. The Vdr locus shows no recombinants with the previously mapped ATP synthase, Atp5k, currently listed at 58 cM in the Chromosome 5 Committee Report map. A genetically-targeted disruption of the Vdr gene has recently been reported [5]. Consideration of the chromosomal position of the targeted locus, and its relationship to the locus encoding the vitamin D binding protein, may be important when strain 129 genome flanking the disrupted Vdr locus is transferred by backcrossing onto various inbred strain backgrounds. Suggestive evidence of linkage of the VDBP/GC locus in humans has been implicated in non-insulin dependent diabetes mellitus (NIDDM). Specific VDBP/GC variants have recently been associated with elevated plasma glucose levels in both Pima Indians and Japanese NIDDM patients [6-8]. QTL analysis of Nidd genes in outcrosses between NZO/Hl females and NON/Lt males has also provided suggestive evidence for a NZO-derived locus controlling blood glucose in the region of Chromosome 5 encompassing the vitamin D binding protein [9]. Given the importance of vitamin D and its metabolites in bone development, as well as normal insulin release and glucose tolerance, the more refined map position of Vdbp (Gc) as well as the discovery of the linkage to the Vdr gene, should contribute to QTL analysis of the control of bone density and glucose homeostasis in mice. 1. Kozak, C, Stephenson, D. (1997). Mamm. Genome 7, S80-S99. 2. Daiger, S, Schanfield, M, Cavalli-Sforza, L. (1975). Proc Natl Acad Sci 72, 2076-2080. 3. Yang, F, Bergeron, J, Linehan, L, Lalley, P, Sakaguchi, A, Bowman, B. (1990). Genomics 7, 509-516. 4. Kozak, C, Stephenson, D. (1997). Mamm. Genome 7, S80-S99. 5. Yoshizawa, T, Handa, Y, Uematsu, Y, Takeda, S, Sekine, K, Yoshihara, Y, Kawakami, T, Arioka, K, Sata, H, Uchiyama, Y, Masushige, S, Fukamizu, A, Matsumoto, T, Kata, S. (1997). Nature Genetics 16, 391-396. 6. Baier, LJ, Thuillez, P, Dobberfuhl, A, Bogardus, C. (1997). Diabetes 46, 170A, and Baier, LJ, Dobberfuhl, A, Hanson, RL, Bogardus, C (199-), Diabetes, manuscript submitted. 7. Pratley, R, Thompson, DB, Prochazka, M, Baier, L, Pima Diabetes Genes Group. (1997). Diabetes 46, 170A. 8. Hirai, M, Suzuki, S, Hinokio, Y, Hiral, A, Chiba, M, Toyota, T. (1997). Diabetes 46, 170A. 9. Leiter, EH, Reifsnyder, PC, Flurkey, K, Partke, H-J, Junger, E, Herberg, L. (199-). J. Clin. Invest., submitted |
