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PMID: 9256466 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

The mouse pale ear (ep) mutation is the homologue of human Hermansky-Pudlak syndrome.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 94 ·No. 17 ·1997-08-19 ·Pages 9238-43

Gardner JM, Wildenberg SC, Keiper NM, Novak EK, Rusiniak ME, Swank RT, Puri N, Finger JN, Hagiwara N, Lehman AL, Gales TL, Bayer ME, King RA, Brilliant MH

Abstract

The recessive mutation at the pale ear (ep) locus on mouse chromosome 19 was found to be the homologue of human Hermansky-Pudlak syndrome (HPS). A positional cloning strategy using yeast artificial chromosomes spanning the HPS locus was used to identify the HPS gene and its murine counterpart. These genes and their predicted proteins are highly conserved at the nucleotide and amino acid levels. Sequence analysis of the mutant ep gene revealed the insertion of an intracisternal A particle element in a protein-coding 3' exon. Here we demonstrate that mice with the ep mutation exhibit abnormalities similar to human HPS patients in melanosomes and platelet-dense granules. These results establish an animal model of HPS and will facilitate biochemical and molecular analyses of the functions of this protein in the membranes of specialized intracellular organelles.

MeSH Terms
Albinism, Oculocutaneous/genetics Amino Acid Sequence Animals Chromosome Mapping Disease Models, Animal Humans Mice Mice, Mutant Strains Molecular Sequence Data Mutation Sequence Alignment Sequence Homology, Amino Acid
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Gardner J M
The Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Wildenberg S C
Keiper N M
Novak E K
Rusiniak M E
Swank R T
Puri N
Finger J N
Hagiwara N
Lehman A L
Gales T L
Bayer M E
King R A
Brilliant M H
References (41)
41 references, click to expand
  1. Pale ear and light ear in the house mouse. Mimic mutations in linkage groups XII and XVII.
    J Hered. 1967 Jan-Feb;58(1):17-20 PMID: 6031677
  2. The intracisternal A-particle gene family: structure and functional aspects.
    Adv Cancer Res. 1988;51:183-276 PMID: 3146900
  3. Lysosomal dysfunctions associated with mutations at mouse pigment genes.
    Genetics. 1979 May;92(1):189-204 PMID: 115747
  4. Hermansky-Pudlak syndrome with granulomatous colitis.
    Ann Intern Med. 1980 Jan;92(1):20-3 PMID: 7350869
  5. Pigmentation and lysosome function in mice homozygous for both pale ear and beige-J pigment genes.
    Genet Res. 1980 Apr;35(2):195-204 PMID: 7390156
  6. Intracellular distribution of lysosomal enzymes in the mouse pigment mutants pale ear and pallid.
    Mol Cell Biochem. 1980 Jun 18;31(2):89-95 PMID: 6774230
  7. Altered secretion of kidney lysosomal enzymes in the mouse pigment mutants ruby-eye, ruby-eye-2-J, and maroon.
    Biochem Genet. 1980 Jun;18(5-6):549-61 PMID: 6776948
  8. The mouse pale ear pigment mutant as a possible animal model for human platelet storage pool deficiency.
    Blood. 1981 Jan;57(1):38-43 PMID: 7448413
  9. The melanin pigmentary disorder in a family with Hermansky-Pudlak syndrome.
    J Invest Dermatol. 1982 Feb;78(2):141-3 PMID: 7057049
  10. Selective proliferation of normal human melanocytes in vitro in the presence of phorbol ester and cholera toxin.
    Proc Natl Acad Sci U S A. 1982 Mar;79(6):2018-22 PMID: 6952249
  11. Hermansky-Pudlak syndrome: a clinicopathologic study.
    Hum Pathol. 1985 Apr;16(4):366-76 PMID: 3980007
  12. Molecular map of chromosome 19 including three genes affecting bleeding time: ep, ru, and bm.
    Mamm Genome. 1994 Jun;5(6):356-60 PMID: 8043950
  13. Mouse Fgf7 (fibroblast growth factor 7) and Fgf8 (fibroblast growth factor 8) genes map to chromosomes 2 and 19 respectively.
    Mamm Genome. 1995 Mar;6(3):196-7 PMID: 7749227
  14. Melanosomes are specialized members of the lysosomal lineage of organelles.
    J Invest Dermatol. 1995 Jul;105(1):3-7 PMID: 7615972
  15. A role for acidic residues in di-leucine motif-based targeting to the endocytic pathway.
    J Biol Chem. 1995 Aug 25;270(34):19989-97 PMID: 7650016
  16. A gene causing Hermansky-Pudlak syndrome in a Puerto Rican population maps to chromosome 10q2.
    Am J Hum Genet. 1995 Oct;57(4):755-65 PMID: 7573033
  17. Linkage disequilibrium mapping of the gene for Hermansky-Pudlak syndrome to chromosome 10q23.1-q23.3.
    Hum Mol Genet. 1995 Sep;4(9):1665-9 PMID: 8541858
  18. Inherited prolonged bleeding time and platelet storage pool deficiency in the subtle gray (sut) mouse.
    Lab Anim Sci. 1996 Feb;46(1):56-60 PMID: 8699821
  19. Pax2, a new murine paired-box-containing gene and its expression in the developing excretory system.
    Development. 1990 Aug;109(4):787-95 PMID: 1977574
  20. Sandy: a new mouse model for platelet storage pool deficiency.
    Genet Res. 1991 Aug;58(1):51-62 PMID: 1936982
  21. Sexual differentiation and regulation of cytochrome P-450 CYP2C7.
    Biochim Biophys Acta. 1992 Jan 9;1118(2):99-106 PMID: 1370375
  22. The mouse pink-eyed dilution gene: association with human Prader-Willi and Angelman syndromes.
    Science. 1992 Aug 21;257(5073):1121-4 PMID: 1509264
  23. Identification of the murine beige gene by YAC complementation and positional cloning.
    Nat Genet. 1996 Jul;13(3):303-8 PMID: 8673129
  24. Identification of the homologous beige and Chediak-Higashi syndrome genes.
    Nature. 1996 Jul 18;382(6588):262-5 PMID: 8717042
  25. Encyclopedia of the mouse genome V. Mouse chromosome 19.
    Mamm Genome. 1996;6 Spec No:S309-16 PMID: 8800775
  26. Molecular markers near the mouse brachymorphic (bm) gene, which affects connective tissues and bleeding time.
    Mamm Genome. 1996 Feb;7(2):98-102 PMID: 8835524
  27. Molecular basis of the pleiotropic phenotype of mice carrying the hypervariable yellow (Ahvy) mutation at the agouti locus.
    Genetics. 1996 Feb;142(2):557-67 PMID: 8852853
  28. Positional cloning of a gene for Hermansky-Pudlak syndrome, a disorder of cytoplasmic organelles.
    Nat Genet. 1996 Nov;14(3):300-6 PMID: 8896559
  29. Identification and mutation analysis of the complete gene for Chediak-Higashi syndrome.
    Nat Genet. 1996 Nov;14(3):307-11 PMID: 8896560
  30. Alternative expression of platelet glycoprotein Ib(beta) mRNA from an adjacent 5' gene with an imperfect polyadenylation signal sequence.
    J Clin Invest. 1997 Feb 1;99(3):520-5 PMID: 9022087
  31. Mouse pale ear (ep) is homologous to human Hermansky-Pudlak syndrome and contains a rare 'AT-AC' intron.
    Hum Mol Genet. 1997 May;6(5):793-7 PMID: 9158155
  32. Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: report of two cases with histochemical studies.
    Blood. 1959 Feb;14(2):162-9 PMID: 13618373
  33. Platelet storage pool deficiency in mouse pigment mutations associated with seven distinct genetic loci.
    Blood. 1984 Mar;63(3):536-44 PMID: 6696991
  34. Effects of ammonia on processing and secretion of precursor and mature lysosomal enzyme from macrophages of normal and pale ear mice: evidence for two distinct pathways.
    J Cell Biol. 1985 Jun;100(6):1894-904 PMID: 3922995
  35. Progenitor cell defect correctable by bone marrow transplantation in five independent mouse models of platelet storage pool deficiency.
    Exp Hematol. 1986 May;14(4):261-5 PMID: 3516713
  36. A new method for predicting signal sequence cleavage sites.
    Nucleic Acids Res. 1986 Jun 11;14(11):4683-90 PMID: 3714490
  37. Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins.
    Annu Rev Biophys Biophys Chem. 1986;15:321-53 PMID: 3521657
  38. Normal murine melanocytes in culture.
    In Vitro Cell Dev Biol. 1987 Jul;23(7):519-22 PMID: 3610949
  39. Reliability of absent platelet dense bodies as a diagnostic criterion for Hermansky-Pudlak syndrome.
    Am J Hematol. 1987 Dec;26(4):305-11 PMID: 3120578
  40. Hermansky-Pudlak syndrome. Ophthalmic findings.
    Ophthalmology. 1988 Apr;95(4):545-54 PMID: 3174014
  41. Synthesis and secretion of kidney beta-galactosidase in mutant le/le mice.
    J Biol Chem. 1978 May 10;253(9):3129-34 PMID: 417081
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.94.17.9238
Published
1997-08-19
Pages
9238-43
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC23134
Subset
IM
Grants
NIGMS NIH HHS · GM22167 · United States
NHLBI NIH HHS · R01 HL031698 · United States
NCI NIH HHS · CA09035 · United States
NIGMS NIH HHS · GM/AR56181 · United States
NCI NIH HHS · P30 CA006927 · United States
NCI NIH HHS · T32 CA009035 · United States
Databases
GENBANK
AF003866, AF003867, AF003868, AF004352, AF004353, U96721, U97149
External Links
PubMed source DOI: 10.1073/pnas.94.17.9238 PMC Full Text View journal details
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