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. 1995 Dec;141(4):1563–1571. doi: 10.1093/genetics/141.4.1563

Molecular Analysis of 36 Mutations at the Mouse Pink-Eyed Dilution (P) Locus

D K Johnson 1, L J Stubbs 1, C T Culiat 1, C S Montgomery 1, L B Russell 1, E M Rinchik 1
PMCID: PMC1206887  PMID: 8601494

Abstract

Thirty-six radiation- or chemically induced homozygous-lethal mutations at the p locus in mouse chromosome 7 have been analyzed at 17 loci defined by molecular probes to determine the types of lesions, numbers of p-region markers deleted or rearranged, regions of overlap of deletion mutations, and genetic distances between loci. A linear deletion map of the [Myod1, Ldh3]-[Snrpn, Znf127] region has been constructed from the molecular analyses of the p-locus deletions. The utility of these deletions as tools for the isolation and characterization of the genes specifying the neurological, reproductive, and developmental phenotypes genetically mapped to this region will grow as more detailed molecular analyses continue.

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Selected References

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  1. Buiting K., Greger V., Brownstein B. H., Mohr R. M., Voiculescu I., Winterpacht A., Zabel B., Horsthemke B. A putative gene family in 15q11-13 and 16p11.2: possible implications for Prader-Willi and Angelman syndromes. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5457–5461. doi: 10.1073/pnas.89.12.5457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buiting K., Neumann M., Lüdecke H. J., Senger G., Claussen U., Antich J., Passarge E., Horsthemke B. Microdissection of the Prader-Willi syndrome chromosome region and identification of potential gene sequences. Genomics. 1990 Mar;6(3):521–527. doi: 10.1016/0888-7543(90)90481-9. [DOI] [PubMed] [Google Scholar]
  3. Buxton J. L., Chan C. T., Gilbert H., Clayton-Smith J., Burn J., Pembrey M., Malcolm S. Angelman syndrome associated with a maternal 15q11-13 deletion of less than 200 kb. Hum Mol Genet. 1994 Aug;3(8):1409–1413. doi: 10.1093/hmg/3.8.1409. [DOI] [PubMed] [Google Scholar]
  4. CATTANACH B. M. A chemically-induced variegated-type position effect in the mouse. Z Vererbungsl. 1961;92:165–182. doi: 10.1007/BF00890283. [DOI] [PubMed] [Google Scholar]
  5. Cattanach B. M., Barr J. A., Evans E. P., Burtenshaw M., Beechey C. V., Leff S. E., Brannan C. I., Copeland N. G., Jenkins N. A., Jones J. A candidate mouse model for Prader-Willi syndrome which shows an absence of Snrpn expression. Nat Genet. 1992 Dec;2(4):270–274. doi: 10.1038/ng1292-270. [DOI] [PubMed] [Google Scholar]
  6. Cattanach B. M. The location of Cattanach's translocation in the X-chromosome linkage map of the mouse. Genet Res. 1966 Oct;8(2):253–256. doi: 10.1017/s0016672300010107. [DOI] [PubMed] [Google Scholar]
  7. Colombo M. P., Martinotti A., Howard T. A., Schneider C., D'Eustachio P., Seldin M. F. Localization of growth arrest-specific genes on mouse chromosomes 1, 7, 8, 11, 13, and 16. Mamm Genome. 1992;2(2):130–134. doi: 10.1007/BF00353861. [DOI] [PubMed] [Google Scholar]
  8. Culiat C. T., Stubbs L. J., Montgomery C. S., Russell L. B., Rinchik E. M. Phenotypic consequences of deletion of the gamma 3, alpha 5, or beta 3 subunit of the type A gamma-aminobutyric acid receptor in mice. Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2815–2818. doi: 10.1073/pnas.91.7.2815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Driscoll D. J., Waters M. F., Williams C. A., Zori R. T., Glenn C. C., Avidano K. M., Nicholls R. D. A DNA methylation imprint, determined by the sex of the parent, distinguishes the Angelman and Prader-Willi syndromes. Genomics. 1992 Aug;13(4):917–924. doi: 10.1016/0888-7543(92)90001-9. [DOI] [PubMed] [Google Scholar]
  10. Eicher E. M. The Position of ru-2 and qv with Respect to the FLECKED Translocation in the Mouse. Genetics. 1970 Mar;64(3-4):495–510. doi: 10.1093/genetics/64.3-4.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Faust C., Schumacher A., Holdener B., Magnuson T. The eed mutation disrupts anterior mesoderm production in mice. Development. 1995 Feb;121(2):273–285. doi: 10.1242/dev.121.2.273. [DOI] [PubMed] [Google Scholar]
  12. Gardner J. M., Nakatsu Y., Gondo Y., Lee S., Lyon M. F., King R. A., Brilliant M. H. The mouse pink-eyed dilution gene: association with human Prader-Willi and Angelman syndromes. Science. 1992 Aug 21;257(5073):1121–1124. doi: 10.1126/science.257.5073.1121. [DOI] [PubMed] [Google Scholar]
  13. Haas M., Ward D. C., Lee J., Roses A. D., Clarke V., D'Eustachio P., Lau D., Vega-Saenz de Miera E., Rudy B. Localization of Shaw-related K+ channel genes on mouse and human chromosomes. Mamm Genome. 1993 Dec;4(12):711–715. doi: 10.1007/BF00357794. [DOI] [PubMed] [Google Scholar]
  14. Johnson D. K., Hand R. E., Jr, Rinchik E. M. Molecular mapping within the mouse albino-deletion complex. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8862–8866. doi: 10.1073/pnas.86.22.8862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kelsey G., Schedl A., Ruppert S., Niswander L., Magnuson T., Klebig M. L., Rinchik E. M., Schütz G. Physical mapping of the albino-deletion complex in the mouse to localize alf/hsdr-1, a locus required for neonatal survival. Genomics. 1992 Oct;14(2):275–287. doi: 10.1016/s0888-7543(05)80217-4. [DOI] [PubMed] [Google Scholar]
  16. Klebig M. L., Kwon B. S., Rinchik E. M. Physical analysis of murine albino deletions that disrupt liver-specific gene regulation or mesoderm development. Mamm Genome. 1992;2(1):51–63. doi: 10.1007/BF00570440. [DOI] [PubMed] [Google Scholar]
  17. Lee S. T., Nicholls R. D., Bundey S., Laxova R., Musarella M., Spritz R. A. Mutations of the P gene in oculocutaneous albinism, ocular albinism, and Prader-Willi syndrome plus albinism. N Engl J Med. 1994 Feb 24;330(8):529–534. doi: 10.1056/NEJM199402243300803. [DOI] [PubMed] [Google Scholar]
  18. Lee S. T., Nicholls R. D., Jong M. T., Fukai K., Spritz R. A. Organization and sequence of the human P gene and identification of a new family of transport proteins. Genomics. 1995 Mar 20;26(2):354–363. doi: 10.1016/0888-7543(95)80220-g. [DOI] [PubMed] [Google Scholar]
  19. Leff S. E., Brannan C. I., Reed M. L., Ozçelik T., Francke U., Copeland N. G., Jenkins N. A. Maternal imprinting of the mouse Snrpn gene and conserved linkage homology with the human Prader-Willi syndrome region. Nat Genet. 1992 Dec;2(4):259–264. doi: 10.1038/ng1292-259. [DOI] [PubMed] [Google Scholar]
  20. Morrow J. F., Stearman R. S., Peltzman C. G., Potter D. A. Induction of hepatic synthesis of serum amyloid A protein and actin. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4718–4722. doi: 10.1073/pnas.78.8.4718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mutirangura A., Jayakumar A., Sutcliffe J. S., Nakao M., McKinney M. J., Buiting K., Horsthemke B., Beaudet A. L., Chinault A. C., Ledbetter D. H. A complete YAC contig of the Prader-Willi/Angelman chromosome region (15q11-q13) and refined localization of the SNRPN gene. Genomics. 1993 Dec;18(3):546–552. doi: 10.1016/s0888-7543(11)80011-x. [DOI] [PubMed] [Google Scholar]
  22. Nakatsu Y., Tyndale R. F., DeLorey T. M., Durham-Pierre D., Gardner J. M., McDanel H. J., Nguyen Q., Wagstaff J., Lalande M., Sikela J. M. A cluster of three GABAA receptor subunit genes is deleted in a neurological mutant of the mouse p locus. Nature. 1993 Jul 29;364(6436):448–450. doi: 10.1038/364448a0. [DOI] [PubMed] [Google Scholar]
  23. Nicholls R. D., Gottlieb W., Russell L. B., Davda M., Horsthemke B., Rinchik E. M. Evaluation of potential models for imprinted and nonimprinted components of human chromosome 15q11-q13 syndromes by fine-structure homology mapping in the mouse. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):2050–2054. doi: 10.1073/pnas.90.5.2050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ozçelik T., Leff S., Robinson W., Donlon T., Lalande M., Sanjines E., Schinzel A., Francke U. Small nuclear ribonucleoprotein polypeptide N (SNRPN), an expressed gene in the Prader-Willi syndrome critical region. Nat Genet. 1992 Dec;2(4):265–269. doi: 10.1038/ng1292-265. [DOI] [PubMed] [Google Scholar]
  25. Potter M. D., Klebig M. L., Carpenter D. A., Rinchik E. M. Genetic and physical mapping of the fitness 1 (fit1) locus within the Fes-Hbb region of mouse chromosome 7. Mamm Genome. 1995 Feb;6(2):70–75. doi: 10.1007/BF00303247. [DOI] [PubMed] [Google Scholar]
  26. Reis A., Dittrich B., Greger V., Buiting K., Lalande M., Gillessen-Kaesbach G., Anvret M., Horsthemke B. Imprinting mutations suggested by abnormal DNA methylation patterns in familial Angelman and Prader-Willi syndromes. Am J Hum Genet. 1994 May;54(5):741–747. [PMC free article] [PubMed] [Google Scholar]
  27. Rinchik E. M., Bultman S. J., Horsthemke B., Lee S. T., Strunk K. M., Spritz R. A., Avidano K. M., Jong M. T., Nicholls R. D. A gene for the mouse pink-eyed dilution locus and for human type II oculocutaneous albinism. Nature. 1993 Jan 7;361(6407):72–76. doi: 10.1038/361072a0. [DOI] [PubMed] [Google Scholar]
  28. Rinchik E. M., Carpenter D. A., Handel M. A. Pleiotropy in microdeletion syndromes: neurologic and spermatogenic abnormalities in mice homozygous for the p6H deletion are likely due to dysfunction of a single gene. Proc Natl Acad Sci U S A. 1995 Jul 3;92(14):6394–6398. doi: 10.1073/pnas.92.14.6394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Rinchik E. M., Carpenter D. A., Long C. L. Deletion mapping of four loci defined by N-ethyl-N-nitrosourea-induced postimplantation-lethal mutations within the pid-Hbb region of mouse chromosome 7. Genetics. 1993 Dec;135(4):1117–1123. doi: 10.1093/genetics/135.4.1117. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rinchik E. M., Carpenter D. A. N-ethyl-N-nitrosourea-induced prenatally lethal mutations define at least two complementation groups within the embryonic ectoderm development (eed) locus in mouse chromosome 7. Mamm Genome. 1993;4(7):349–353. doi: 10.1007/BF00360583. [DOI] [PubMed] [Google Scholar]
  31. Russell L. B., Montgomery C. S., Cacheiro N. L., Johnson D. K. Complementation analyses for 45 mutations encompassing the pink-eyed dilution (p) locus of the mouse. Genetics. 1995 Dec;141(4):1547–1562. doi: 10.1093/genetics/141.4.1547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Russell L. B., Montgomery C. S., Raymer G. D. Analysis of the albino-locus region of the mouse: IV. Characterization of 34 deficiencies. Genetics. 1982 Mar;100(3):427–453. doi: 10.1093/genetics/100.3.427. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Scrable H. J., Johnson D. K., Rinchik E. M., Cavenee W. K. Rhabdomyosarcoma-associated locus and MYOD1 are syntenic but separate loci on the short arm of human chromosome 11. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2182–2186. doi: 10.1073/pnas.87.6.2182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sharan S. K., Holdener-Kenny B., Ruppert S., Schedl A., Kelsey G., Rinchik E. M., Magnuson T. The albino-deletion complex of the mouse: molecular mapping of deletion breakpoints that define regions necessary for development of the embryonic and extraembryonic ectoderm. Genetics. 1991 Nov;129(3):825–832. doi: 10.1093/genetics/129.3.825. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Spritz R. A. Molecular genetics of oculocutaneous albinism. Hum Mol Genet. 1994;3(Spec No):1469–1475. doi: 10.1093/hmg/3.suppl_1.1469. [DOI] [PubMed] [Google Scholar]
  36. Stoll J., Kozak C. A., Goldman D. Characterization and chromosomal mapping of a cDNA encoding tryptophan hydroxylase from a mouse mastocytoma cell line. Genomics. 1990 May;7(1):88–96. doi: 10.1016/0888-7543(90)90522-v. [DOI] [PubMed] [Google Scholar]
  37. Stubbs L., Rinchik E. M., Goldberg E., Rudy B., Handel M. A., Johnson D. Clustering of six human 11p15 gene homologs within a 500-kb interval of proximal mouse chromosome 7. Genomics. 1994 Nov 15;24(2):324–332. doi: 10.1006/geno.1994.1623. [DOI] [PubMed] [Google Scholar]
  38. Ullrich A., Gray A., Tam A. W., Yang-Feng T., Tsubokawa M., Collins C., Henzel W., Le Bon T., Kathuria S., Chen E. Insulin-like growth factor I receptor primary structure: comparison with insulin receptor suggests structural determinants that define functional specificity. EMBO J. 1986 Oct;5(10):2503–2512. doi: 10.1002/j.1460-2075.1986.tb04528.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Wagstaff J., Knoll J. H., Fleming J., Kirkness E. F., Martin-Gallardo A., Greenberg F., Graham J. M., Jr, Menninger J., Ward D., Venter J. C. Localization of the gene encoding the GABAA receptor beta 3 subunit to the Angelman/Prader-Willi region of human chromosome 15. Am J Hum Genet. 1991 Aug;49(2):330–337. [PMC free article] [PubMed] [Google Scholar]
  40. Zhou W., Xu J., Goldberg E. A 60-bp core promoter sequence of murine lactate dehydrogenase C is sufficient to direct testis-specific transcription in vitro. Biol Reprod. 1994 Sep;51(3):425–432. doi: 10.1095/biolreprod51.3.425. [DOI] [PubMed] [Google Scholar]

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