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Localization of the murine cholecystokinin A and B receptor genes

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Abstract

We have determined the chromosomal locations of the two cholecystokinin (CCK) receptor genes in the mouse. Genetic localization utilized an interspecific backcross panel formed from the cross (C57BL/6J x Mus spretus) F1 x Mus spretus. Genomic DNAs from 94 individuals in the backcross were analyzed by Southern hybridization with rat CCKA and CCKB receptor cDNA probes. Unique map positions were determined by haplotype analysis with 650 previously mapped loci in the mouse backcross. The CCKA receptor gene (Cckar) mapped to mouse Chromosome (Chr) 5, in tight linkage with the DNA marker D5Bir8. The CCKB receptor gene (Cckbr) mapped to mouse Chr 7, tightly linked to the β-hemoglobin locus (Hbb). This localization places Cckbr in the same region as the mouse obesity mutation tubby (tub), which also maps near Hbb (2.4±1.4 cM). Since CCK can function as a satiety factor when administered to rodents, localization of Cckbr near the tub mutation identifies this receptor as a possible candidate gene for this obesity mutation.

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References

  • Baile, C.A., McLaughlin, C.L., Della-Fera, M.A. (1986). Role of cholecystokinin and opioid peptides in control of food intake. Physiol. Rev. 66, 172–234.

    Google Scholar 

  • Coleman, D.L., Eicher, E.M. (1990). Fat (fat) and tubby (tub): two autosomal recessive mutations causing obesity syndromes in the mouse. J. Hered. 81, 424–427.

    Google Scholar 

  • Cooper, S.J., Dourish, C.T. (1990). Multiple cholecystokinin (CCK) receptors and CCK-monamine interactions are instrumental in the control of feeding. Physiol. Behav. 48, 849–857.

    Google Scholar 

  • Della-Fera, M.A., Baile, C.A. (1979). Cholecystokinin octapeptide-continuous picomole injection in the cerebral ventricles of sheep suppress feeding. Science 206, 471–473.

    Google Scholar 

  • de Weerth, A., Pisegna, J.R., Huppi, K., Wank, S.A. (1993). Molecular cloning, functional expression and chromosomal localization of the human cholecystokinin type A receptor. Biochem. Biophys. Res. Commun. 194, 811–818.

    Google Scholar 

  • Dietrich, W.R., Miller, J.C., Steen, R.G., Merchant, M., Damron, D., Nahf, R., Gross, A., Joyce, D.C., Wessel, M., Dredge, R.D., Marquis, A., Stein, L.D., Goodman, N., Page, D.C., Lander, E.S. (1994). A genetic man of the mouse with 4,006 simple sequence length polymorphisms. Nature Genet. 7, 220–245.

    Google Scholar 

  • Dizik, M., Elliott, R.W. (1977). A gene apparently determining the extent of sialylation of lysosomal α-mannosidase in mouse liver. Biochem. Genet. 15, 31–46.

    Google Scholar 

  • Dourish, C.T., O'Neill, M.F., Coughlan, J., Kitchener, S.J., Hawley, D., Iversen, S.D. (1990). The selective CCK-B receptor antagonist L-365,260 enhances morphine analgesia and prevents morphine tolerance in the rat. Eur. J. Pharmacol. 176, 35–44.

    Google Scholar 

  • Feinberg, A.P., Vogelstein, B. (1983). A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal. Biochem. 132, 6–13

    Google Scholar 

  • Friedman, J.M., Leibel, R.L., Bahary, N. (1991). Molecular mapping of obesity genes. Mamm. Genome 1, 130–144.

    Google Scholar 

  • Gibbs, J., Smith, G.P. (1986). Gut peptides and feeding behavior: the model of cholecystokinin. in Feeding Behavior Neural and Humoral Controls, R.C. Ritter, S. Ritter, C.D. Barnes, eds (New York: Academic Press), pp. 329–352.

    Google Scholar 

  • Gibbs, J., Young, R.C., Smith, G.P. (1973). Cholecystokinin decreases food intake in rats. J. Comp. Physiol. Psychol. 84, 488–495.

    Google Scholar 

  • Holdener, B.C., Brown, S.D.M., Angel, J.M., Nicholls, R.D., Kelsey, G., Magnuson, T. (1993). Mouse Chromosome 7. Mamm. Genome 4 (suppl.), S110-S120.

    Google Scholar 

  • Hughes, J., Boden, P., Costall, B., Domeney, A., Kelly, E., Horwell, D.C., Hunter, J.C., Pinnock, R.D., Woodruff, G.N. (1990). Development of a class of selective cholecystokinin type B receptor antagonists having potent anxiolytic activity. Proc. Natl. Acad. Sci. USA 87, 6728–6732.

    Google Scholar 

  • Innis, R.B., Snyder, S.H. (1980). Distinct cholecystokinin receptors in brain and pancreas. Proc. Natl. Acad. Sci. USA 77, 6917–6921.

    Google Scholar 

  • Jenson, R.T., Wank, S.A., Rowley, W.H., Sato, S., Gardner, J.D. (1989). Interaction of CCK with pancreatic acinar cells. Trends Pharmacol. Sci. 10, 418–423.

    Google Scholar 

  • Jones, J.M., Meisler, M.H., Seldin, M.F., Lee, B.K., Eicher, E.M. (1992). Localization of insulin-2 (Ins-2) and the obesity mutant tubby (tub) to distinct regions of mouse chromosome 7. Genomics 14, 197–199.

    Google Scholar 

  • Kopin, A.S., Lee, Y.-M., mcBride, E.W., Miller, L.J., Lu, M., Lin, H.Y., Kolakowski, L.F., Beinborn, M. (1992). Expression cloning and characterization of the canine parietal cell gastrin receptor. Proc. Natl. Acad. Sci. USA 89, 3605–3609.

    Google Scholar 

  • Kozak, C.A., Stephenson, D.A. (1993). Mouse Chromosome 5. Mamm. Genome 4 (Suppl.), S72-S87.

    Google Scholar 

  • Kopin, A.S. (1993). The human brain cholecystokinin-B/gastrin receptor. J. Biol. Chem. 268, 8164–8169.

    Google Scholar 

  • Moran, T.H., Amegloi, P.J., Schwartz, G.J., McHugh, P.R. (1992). Blockage of type A, not type B, CCK receptors attenuates satiety actions of exogenous and endogenous CCK. Am. J. Physiol. 262, R46-R50.

    Google Scholar 

  • Nakata, H., Matsui, T., Ito, M., Taniguchi, T., Naribayashi, Y., Arima, N., Nakamura, A., Kinoshita, Y., Chihara, K., Hosoda, S., Chiba, T. (1992). Cloning and characterization of gastrin receptor from ECL carcinoid tumor of Mastomys natalensis. Biochem. Biophys. Res. Commun. 187, 1151–1157.

    Google Scholar 

  • Pisegna, J.R., de Weerth, A., Huppi, K., Wank, S.A. (1992). Molecular cloning of the human brain and gastric cholecystokinin receptor: structure, functional expression and chromosomal location. Biochem. Biophys. Res. Commun. 189, 296–303.

    Google Scholar 

  • Rowe, L.B., Nadeau, J.H., Turner, R., Frankel, W.N., Letts, V.A., Eppig, J.T., Ko, M.S.H., Thurston, S.J., Birkenmeier, E.H. (1994). Maps from two interspecific backcross DNA panels available as a community genetic mapping resource. Mamm. Genome 5, 253–274.

    Google Scholar 

  • Schick, R.R., Schusdziarra, V., Yaksh, T.L., Go, V.L.W. (1994). Brain regions where cholecystokinin exerts its effect on satiety. Ann. N.Y. Acad. Sci. 713, 242–254.

    Google Scholar 

  • Silver, A.J., Flood, J.F., Song, A.M., Morley, J.E. (1989). Evidence for a physiological role for CCK in the regulation of food intake in mice. Am. J. Physiol. 256. R646-R652.

    Google Scholar 

  • Singh, L., Lewis, A.S., Field, M.J., Hughes, J., Woodruff, G.N. (1991). Evidence for an involvement of the brain cholecystokinin B receptor in anxiety. Proc. Natl. Acad. Sci. USA 88, 1130–1133.

    Google Scholar 

  • Smith, G.P., Jerome, C., Norgue, R. (1985). Afferent axons in abdominal vagus mediate satiety effect of cholecystokinin in rats. Am. J. Physiol. 245, R638-R641.

    Google Scholar 

  • Song, I., Brown, D.R., Wiltshire, R.N., Gantz, I., Trent, J.M., Yamada, T. (1993). The human gastrin/cholecystokinin type B receptor gene: alternative splice donor site in exon 4 generates two variant mRNAs. Proc. Natl. Acad. Sci. USA 90, 9085–9089.

    Google Scholar 

  • Ulrich, C.D., Ferber, I., Holicky, E., Hadac, E., Buell, G., Miller, L.J. (1993). Molecular cloning and functional expression of the human gallbladder cholecystokinin A receptor. Biochem. Biophys. Res. Commun. 193, 204–211.

    Google Scholar 

  • Wank, S.A., Harkins, R., Jensen, R.T., Shapira, H., de Weerth, A., Stattery, T. (1992a). Purification, molecular cloning, and functional expression of the cholecystokinin receptor from rat pancreas. Proc. Natl. Acad. Sci. USA. 89, 3125–3129.

    Google Scholar 

  • Wank, S.A., Pisegna, J.R., de Weerth, A. (1992b). Brain and gastrointestinal cholecystokinin receptor family: structure and functional expression. Proc. Natl. Acad. Sci. USA 89, 8691–8695.

    Google Scholar 

  • Weatherford, S.C., Chiruzzo, R.Y., Laughton, W.B. (1992). Satiety induced by endogenous and exogenous cholecystokinin is mediated by CCK-A receptors in mice. Am. J. Physiol. 262, R574-R578.

    Google Scholar 

  • Wiesenfeld-Hallin, Z., Xu, X.-J., Hughes, J., Horwell, D.C., Hokfelt, T. (1990). PD134308, a selective antagonist of cholecystokinin type B receptor, enhances the analgesic effect of morphine and synergistically interacts with intrathecal galanin to depress spinal nociceptive reflexes. Proc. Natl. Acad. Sci. USA 87, 7105–7109.

    Google Scholar 

  • Zimonjic, D.B., Popescu, N.C., Matsui, T., Ito, M., Chihara, K. (1994). Localization of the human cholecystokinin-B/gastrin receptor gene (CCKBR) to Chromosome 11p15.5–p15.4 by fluorescence in situ hybridization. Cytogenet. Cell Genet. 65, 184–185.

    Google Scholar 

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Authors and Affiliations

  1. Department of Physiology, University of Michigan, 7761 Medical Science II, 48109-0622, Ann Arbor, Michigan, USA

    L. C. Samuelson, M. S. Isakoff & K. A. Lacourse

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  1. L. C. Samuelson
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  2. M. S. Isakoff
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  3. K. A. Lacourse
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Samuelson, L.C., Isakoff, M.S. & Lacourse, K.A. Localization of the murine cholecystokinin A and B receptor genes. Mammalian Genome 6, 242–246 (1995). https://doi.org/10.1007/BF00352408

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  • DOI: https://doi.org/10.1007/BF00352408

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