Abstract
We describe the genetic mapping of hyperphenylalaninemia 2 (hph2), a recessive mutation in the mouse that causes deficient amino acid transport similar to Hartnup Disorder, a human genetic amino acid transport disorder. The hph2 locus was mapped in three separate crosses to identify candidate genes for hph2 and a region of homology in the human genome where we propose the Hartnup Disorder gene might lie. The mutation maps to mouse Chromosome (Chr) 7 distal of the simple sequence length polymorphism (SSLP) marker D7Mit140 and does not recombine with D7Nds4, an SSLP marker in the fibroblast growth factor 3 (Fgf3) gene. Unexpectedly, the mutant chromosome affects recombination frequency in the D7Mit12 to D7Nds4 interval.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Arriza JL, Kavanaugh MP, Fairman, WA, Wu Y-N, Murdoch GH, North RA, Amara SG (1993) Cloning and expression of a human neutral amino acid transporter with structural similarity to the glutamate transporter gene family. J Biol Chem 268, 15329–15332
Barlow DP (1994) Imprinting: a gamete’s point of view. Trends Genet 10, 194–199
Baron DN, Dent CE, Harris H, Hart EW, Jepson JB (1956) Hereditary pellagra-like skin rash with temporary cerebellar ataxia, constant renal amino-aciduria, and other bizarre biochemical features. Lancet 2, 421–428
Calonge MJ, Gasparini P, Chillaron J, Gallucci M, Rousaud F, Zelante L, Testar X, Dallapiccola B, DiSilverio F, Barcelo P, Estivill X, Zorzano A, Nunes V, Palacin M (1994) Cystinuria caused by mutations in rBAT, a gene involved in the transport of cystine. Nature Genet 6, 420–425
Cattanach BM, Beechey CV (1985) Differential activity of maternally and paternally derived chromosome regions in mice. Nature 315, 496–498
Copeland NG, Gilbert DJ, Jenkins NA, Nadeau JH, Eppig JT, Maltais LJ, Miller JC, Dietrich WF, Steen RG, Lincoln SE, Weaver A, Joyce DC, Merchant M, Wessel M, Katz H, Stein LD, Reeve MP, Daly MJ, Dredge RD, Marquis A, Goodman N, Lander ES (1993) Genome Maps IV. Science 262, 67
Debry RW, Seldin MF (1996) Human/Mouse Homology Relationships, National Center for Biotechnology Information. World Wide Web (URL: http://www3.ncbi.nlm.nih.gov/Homology/)
Dietrich WF, Miller JC, Steen RG, Merchant M, Damron D, Nahf R, Gross A, Joyce DC, Wessel M, Dredge RD, Marquis A, Stein LD, Goodman N, Page DC, Lander ES (1994) A genetic map of the mouse with 4006 simple sequence length polymorphisms. Nature Genet 7, 220–245
Supplemented by additional markers in: Whitehead Institute/MIT Center for Genome Research, Genetic Map of the Mouse, Database (http:// www-genome.wi.mit.edu) Release 10, June 1996
Dietrich WF, Miller J, Steen R, Merchant MA, Damron-Boles D, Husain Z, Dredge R, Daly MJ, Ingalls KA, O’Conner TJ, Evans CA, DeAngelis MM, Levinson DM, Kruglyak L, Goodman N, Copeland NG, Jenkins NA, Hawkins TL, Stein L, Page DC, Lander ES (1996) A comprehensive genetic map of the mouse genome. Nature 380, 149–152
Julier C, Nakamura Y, Lathrop M, O’Connell P, Leppert M, Litt M, Mohandas T, Lalouel J-M, White R (1990) A detailed genetic map of the long arm of chromosome 11. Genomics 7, 335–345
Krugylak L, Daly MJ, Lander ES (1995) Rapid multipoint linkage analysis of recessive traits in nuclear families, including homozygosity mapping. Am J Hum Genet 56, 519–527
Lammie GA, Smith R, Silver J, Brookes S, Dickson C, Peters G (1992) Proviral insertions near the cyclin D1 gene in mouse lymphomas: a parallel for BCL1 translocations in human B-cell neoplasms. Oncogene 7, 2381–2387
Lee W-S, Wells RB, Sabbag RV, Mohandas TK, Hediger MA (1993) Cloning and chromosomal localization of a human kidney cDNA involved in cystine, dibasic, and neutral amino acid transport. J Clin Invest 91, 1959–1963
Les EP (1996) Husbandry. In Biology of the Laboratory Mouse, EL Green, ed (New York: McGraw-Hill), pp 29–37
Levy HL (1995) Hartnup Disorder. In Metabolic and Molecular Bases of Inherited Disease, CR Scriver, AL Beaudet, WS Sly, D Valle, eds (New York: McGraw-Hill), pp 3629–3642
Litt M, Kramer P, Hauge XY, Weber JL, Wang Z, Wilkie PJ, Holt MS, Mishra S, Donis-Keller H, Warnich L, Retief AE, Jones C, Weissenbach J (1993) A microsatellite-based index map of human chromosome 11. Hum Mol Genet 2, 909–913
McDonald JD, Bode VC (1988) Hyperphenylalaninemia in the hph-1 mouse mutant. Pediatr Res 23 63–67
McDonald JD, Bode VC, Dove WF, Shedlovsky A (1990) Pahhph-5: a mouse mutant deficient in phenylalanine hydroxylase. Proc Natl Acad Sci USA 87, 1965–1967
McGivan JD, Pastor-Anglada M (1994) Regulatory and molecular aspects of mammalian amino acid transport. Biochem J 299, 321–334
Mouse Genome Database (MGD) 3.1, Mouse Genome Informatics, The Jackson Laboratory, Bar Harbor, Maine. World Wide Web (URL: http:/ www.informatics.jax.org/). (February 1996)
Phillips S, Nadeau J (1984) Mouse News Letter 70, 83
Pontoglio M, Barra J, Hadchouel M, Doyen A, Kress C, Bach JP, Babinet C (1996). Hepatocyte nuclear factor 1 inactivation results in hepatic dysfunction, phenylketonuria and renal Fanconi syndrome. Cell 84, 575–585
Pras E, Arber N, Aksentijevich I, Katz G, Schapiro JM, Prosen L, Gruberg L, Harel D, Liberman U, Weissenbach J, Pras M, Kastner DL (1994) Localization of a gene causing cystinuria to chromosome 2p. Nature Genet 6, 415–419
Quinlan DC, Hochstadt J (1977) The regulation by fibroblast growth factor of early transport changes in quiescent 3T3 cells. J Cell Physiol 93, 237–246
Reizer J, Reizer A, Saier MH (1994) A functional superfamily of sodium/ solute symporters. Biochim Biophys Acta 1197, 133–166
Rosier M-F, Reguigne-Arnould I, Coullin P, Devignes M-D, Auffray C (1995) Regional assignment of 68 new human gene transcripts on chromosome 11. Genome Res 5, 60–70
Saier MH (1994) Convergence and divergence in the evolution of transport proteins. BioEssaya 16, 23–29
Scriver CR (1988) Nutrient-gene interactions: the gene is not the disease and vice-versa. Am J Clin Nutr 48, 1505–1509
Searle AG, Beechey CV (1990) Genome imprinting phenomena on mouse chromosome 7. Genet Res 56, 237–244
Shafqat S, Tamarappoo BK, Kilberg MS, Puranam RS, McNamara JO, Guadano-Ferraz A, Fremeau RT (1993) Cloning and expression of a novel Na+-dependent neutral amino acid transporter structurally related to mammalian Na+/glutamate cotransporters. J Biol Chem 268, 15351–15355
Shedlovsky A, McDonald JD, Symula D, Dove WF (1993) Mouse models of human phenylketonuria. Genetics 134, 1205–1210
Silver J, Buckler CE (1986) Statistical considerations for linkage analysis using recombinant inbred strains and backcrosses. Proc Natl Acad Sci USA 83, 1423–1427
Symula DJ, Shedlovsky A, Guillery EN, Dove WF (1996) A candidate mouse model for Hartnup disorder deficient in neutral amino acid transport. Mamm Genome 8, 102–107
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Symula, D.J., Shedlovsky, A. & Dove, W.F. Genetic mapping of hph2, a mutation affecting amino acid transport in the mouse. Mammalian Genome 8, 98–101 (1997). https://doi.org/10.1007/s003359900366
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s003359900366