Strain Detail Sheet

Genetic Alterations:
1 kb (H2A histone) insertion in the Hps5 gene. The insertion is in exon 18 immediately preceeding codon 868.

Genotype Determination:

ES Cell Line: Not Applicable

Phenotype
In addition to hypopigmentation, lysosomes and platelets are functionally abnormal. Eye color for homozygous mice is red, then darkens to ruby; Wildtype and Heterozygous eye color is black

In mice, at least 16 HPS genes have been identified. They are involved with maturation of lysosomal-related organelles, including pigment cells, and most are components of specific protein complexes, BLOC-1 (pallid, cappuccino, muted loci), BLOC-2 (ruby eye and ruby eye-2 and cocoa), BLOC-3 and BLOC-4 (HPS1/pale ear and HPS4/light ear). HPS genes function in the biogenesis of lysosomes and lysosome-related cell-specific organelles such as melanosomes (found in pigment cells in skin, eye, ear, and meninges), platelet dense granules, and lung lamellar bodies. The major pathologic conditions associated with HPS are oculocutaneous albinism, prolonged bleeding, cellular accumulation of ceroid-like pigment, and pulmonary fibrosis.

Ruby2 is a member of the BLOC-2 complex and is the result of a spontaneous mutant that arose in a substrain of C57BL. An insertion of a 1.0 kb fragment of H2f2a that contains an 8 nt duplication at the 3' end was identified immediately upstream of codon 868 (exon 18).

Mammalian Phenotype Terms:(provided by MGI)      Extend all MPTs
      assigned by genotype

Hps5^ru2/Hps5^ru2

        C57BL

• pigmentation phenotype
  • diluted coat color (MGI Ref ID J:20282)
    • described as similar to the ruby-eye (ru) mutation
• integument phenotype
  • diluted coat color (MGI Ref ID J:20282)
    • described as similar to the ruby-eye (ru) mutation

Hps5^ru2/Hps5^ru2

        involves: C57BL

• pigmentation phenotype
  • abnormal eye pigmentation (MGI Ref ID J:81444)
    • electron microscopy shows that there are fewer melanocytes in the retinal pigment epithelium and choroid, the remaining melanocytes in the retinal pigment epithelium are often disorganized and those in the choroid often have ragged outlines instead of the normal smooth exterior membranes and are often clumped within large multimelanosomal bodies
    • abnormal choroid pigmentation (MGI Ref ID J:81444)
    • abnormal pigment epithelium of the eye (MGI Ref ID J:81444)
• vision/eye phenotype
  • abnormal eye pigmentation (MGI Ref ID J:81444)
    • electron microscopy shows that there are fewer melanocytes in the retinal pigment epithelium and choroid, the remaining melanocytes in the retinal pigment epithelium are often disorganized and those in the choroid often have ragged outlines instead of the normal smooth exterior membranes and are often clumped within large multimelanosomal bodies
    • abnormal choroid pigmentation (MGI Ref ID J:81444)
    • abnormal pigment epithelium of the eye (MGI Ref ID J:81444)

Founder genetic background: C57BL

Strain genetic background: C57BL/6J

Strain Development: This mutation arose spontaneously in a C57BL/6 mouse. This mutation has been bred to homozygosity.

Suggested Control Mice:

• C57BL/6J

• Developmental Biology
• Hermansky Pudlak Syndrome (HPS)
• Organelle Structure and Function
• Pigmentation
• Oculocutaneous albinism
• Prolonged Bleeding
• Pulmonary Fibrosis
• Platelet Dense Granules
• Lung Development

Donor: Lynn Lamoreux, Ph.D., Texas A & M University

Primary Reference:

• Zhang Q, Zhao B, Li W, Oiso N, Novak EK, Rusiniak ME, Gautam R, Chintala S, O'Brien EP, Zhang Y, Roe BA, Elliott RW, Eicher EM, Liang P, Kratz C, Legius E, Spritz RA, O'Sullivan TN, Copeland NG, Jenkins NA, Swank RT. Ru2 and Ru encode mouse orthologs of the genes mutated in human Hermansky-Pudlak syndrome types 5 and 6. Nat Genet. 2003 Feb;33(2):145-53. Epub 2003 Jan 27. (Medline PMID: 12548288)
• Gautam R, Chintala S, Li W, Zhang Q, Tan J, Novak EK, Di Pietro SM, Dell'Angelica EC, Swank RT. The Hermansky-Pudlak syndrome 3 (cocoa) protein is a component of the biogenesis of lysosome-related organelles complex-2 (BLOC-2). J Biol Chem. 2004 Mar 26;279(13):12935-42. Epub 2004 Jan 12. (Medline PMID: 14718540)
• Nguyen T, Novak EK, Kermani M, Fluhr J, Peters LL, Swank RT, Wei ML. Melanosome morphologies in murine models of hermansky-pudlak syndrome reflect blocks in organelle development. J Invest Dermatol. 2002 Nov;119(5):1156-64. PMID: 12445206 (Medline PMID: 12445206)

Coat color: Homozygous are gray; Wildtype and Heterozygous are black

Other:

MMRRC Breeding System: Sib Mating

Breeding Scheme(s):

• Homozygous female x Homozygous male
• Homozygous female x Heterozygous/Wildtype male
• Heterozygous/Wildtype female x Homozygous male

Generation: N10+F5+ As of: 4/20/04

Overall Breeding Performance: Good

Average litter size: 7

Recommended wean age: 3-4 weeks

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@missouri.edu.