Galanin receptor 1 gene (Galnr1) is tightly linked to the myelin basic protein gene on Chromosome 18 in mouse

Galanin receptor 1 gene (Galnr1) is tightly linked to the myelin basic protein gene on Chromosome... Mammalian Genome 8, Brief Data Reports 875 Galanin receptor 1 gene (Galnrl) is tightly linked to the myelin basic protein gene on Chromosome 18 in mouse Denise K. Simoneaux, 1 Robin J. Leach, 2 Peter O'Connell l'z ~Department of Pathology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78284, USA 2Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas, 78284, USA Fig. 1. Mapping of Galnrl to mouse Chr 18. (A) Southern blot of a Taql restriction digest of M spretus (S), C57BL/6J (B), and (M. spretus x Received: 3 June 1997 / Accepted: 8 July 1997 C57BL/6J)F 1 heterozygous (BS) genomic DNAs hybridized with the rat Species: Mouse GALNR cDNA. (B) Haplotype analysis of the (M. spretus x C57BL/6J)F 1 Locus name: Galanin receptor 1 x M. spretus backcross panel showing the position of Galnrl in relation to Locus symbol: Gatnrl other genes and markers on Chr 18. Solid boxes indicate the inheritance of the C57BL/6J allele, and open boxes indicate the inheritance of the M. Map position: Chromosome (Chr) 18 at 55 cM spretus allele from the F~ parent. Method of mapping: The interspecies backcrosses (M. spretus x C57BL/6J)F 1 x M. spretus and M. spretus � C57BL/6J)F 1 x Corp., and NIH postdoctoral fellowship 5 F32 HG00164-02 to D.K. Si- C57BL/6J (Jackson Lab Backcross Panels BSS and BSB) con- moneaux. sisted of 94 animals each. Data deposit information: MGD-JNUM-38577 References Molecular reagent: A 1.59-kilobase (kb) rat cDNA containing the 1. Nicholl J, Kofler B, Sutherland GR, Shire J, Iismaa TP (1995) As- entire coding region for galanin receptor 1. signment of the gene encoding human galanin receptor (GALNR) to Method of allele detection: A Taql restriction fragment length 18q23 by in situ hybridization. Genomics 30, 629-630 polymorphism (RFLP) was detected by the presence of a 6.5-kb 2. Cody JD, Pierce JF, Brkanac Z, Plaetka R, Ghidon PD, Kaye CI, and 2.5-kb genomic DNA fragment in M. spretus and by 7.1-kb Leach RJ (1997) Growth hormone insufficiency associated with hap- loinsufficiency at 18q23. Am J Med Genet, 169, 280-286 and 2.8-kb fragments in C57BL/6J. 3. Amiranoff B, Loriner AM, Lagny-Pourmir I, LaBurthe M (1988) Previously identified homologs- Human GALNR1 was mapped to Mechanism of galanin-inhibited insulin release: occurrence of a per- 18q23 by fluorescence in situ hybridization [1] and by physical tussis-toxin-sensitive inhibition of adenylate cyclase. Eur J Biochem mapping [2]. 177, 147-152 Discussion: Galanin receptor (GALNR1) is a G-protein coupled 4. Homaidan FR, Sharp GW, Nowak LM (1991) Galanin inhibits a di- receptor linked to voltage gated calcium channels [3-5]. The hydropyridine-sensitive Ca z§ current in the RINm5f cell line. Proc GALNR1 ligand is galanin, a 29-amino acid neuropeptide widely Natl Acad Sci USA 88, 8744-8748 distributed in the central and peripheral nervous systems of nu- 5. De Weille JH, Fosset M, Schmid-Antonmarchi H, Ladunski M (1989) Galanin inhibits dopamine secretion and activates a potassium channel merous species [6]. Galanin controls endocrine and exocrine pan- in pheochromocytoma cells. Brain Res 485, 199-203 creatic secretions, regulates intestinal motility, modulates behav- 6. Merchenthaler L, Lopez FJ, Negro-Vilar A (1993) Anatomy and ioral, cognitive, and sensory functions, and may modulate growth physiology of central galanin-containing pathways. Progr Neurobiol hormone secretion [7]. 40, 711-769 Despite strong evidence of extensive homology between 7. Bedecs K, Berthold M, Bartfai T (1995) Galanin--ten years with a mouse and human Chr 18, only seven human chromosome 18q loci neuroendocrine peptide. Int J Biochem Cell Biol 27, 337-349 have been comparatively mapped in these two species. To localize 8. Strathdee G, Zackai, EH, Shapiro R, Kamholz J, Overhauser J (1995) the mouse Galnrl gene, we analyzed the segregation of an RFLP Analysis of clinical variation seen in patients with 18q terminal dele- in DNAs derived from the offspring of The Jackson Lab BSS and tions. Am J Med Genet 59, 476--483 BSB backcross panels [10]. Figure 1A shows a TaqI RFLP de- 9. Ghidoni PD, Hale DE, Cody JD, Thompson NM, McClure EB, Gray CT, Danney MM, Leach RJ, Kaye CI (1996) Growth hormone defi- tected with a rat galanin receptor cDNA probe, consisting of 6.5- ciency associated with 18q deletion syndrome. Am J Med Genet 69, kb and 2.5-kb M. spretus genomic DNA fragments and 7.1-kb and 1-12 2.8-kb C57BL/6J genomic fragments. Haplotype analysis of the 10. Rowe L, Nadeau JH, Turner R, Frankel WN, Letts HS, Eppig JJ, Ko backcross panel data showed no recombinants between Mbp and MS, Thurston S J, Birkenmeier EH (1994) Maps from two interspecific Galnrl, indicating complete linkage between these two genes. backcross DNA panels as community mapping resource. Mamm Ge- Tight linkage between MBP and GALNR1 is also observed on nome 5, 253-274 human Chr 18q based on co-location of these two genes on YAC clones 809_B_4 and 776_F_5 [2]. The region around MBP has been implicated as a region involved in the growth hormone in- The Jagged2 gene maps to Chromosome 12 sufficiency phenotype of patients with Chr 18q-syndrome [2,8,9]. and is a candidate for the lgl and By correlating genotype with phenotype in affected children, it sm mutations should be possible to determine whether GALNR1 or MBP is responsible for specific 18q-syndrome phenotypic features. Yu Lan, 1 Rulang Jiang, 1 Carrie Shawber, 2 Acknowledgments: We thank Kathleen Sullivan of Merck for the rat Gerry Weinmaster, z Thomas Gridley 1 GALNR1 cDNA and Lucy Rowe of The Jackson Lab Mouse Mapping Resource. This work was supported by the MacDonald family, Microsoft 1The Jackson Laboratory, 600 Main Street, Bar Harbor, Maine 04609, USA 2Department of Biological Chemistry, UCLA School of Medicine, Los Angeles, California 90024, USA Correspondence to: P. O'Connell Mammalian Genome Springer Journals

Galanin receptor 1 gene (Galnr1) is tightly linked to the myelin basic protein gene on Chromosome 18 in mouse

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