B6.C3-Pde6b^rd1 Hps4^le/J

Stock number: 000002
Research areas: Cardiovascular Research, Dermatology Research, Hematological Research, Internal/Organ Research, Mouse/Human Gene Homologs, Sensorineural Research

Description

Light-ear (le) is a spontaneous mutation in Hps4 (Hermansky-Pudlak syndrome 4 homolog (human)) that maybe be useful as a model for Hermansky-Pudlak syndrome. Homozygous mice are characterized by light ears, tail and feet, a platelet storage pool deficiency resulting in prolonged bleeding times and accumulation of lysosomal enzymes in the kidney. This congenic also is homozygous for the retinal degeneration 1 (Pde6b^rd1) allele, a characteristic of C3H substrains, and located in close proximity to light-ear on Chr 5.

Detailed description

Hps4 (Hermansky-Pudlak syndrome 4 homolog (human)) encodes a protein that is a component of the lysosomal complex BLOC3. Mutations in HPS4 are associated with one form of Hermansky-Pudlak syndrome, a human disorder that includes oculocutaneous albinism, platelet storage pool defects and lysosomal ceroid accumulation. Mice homozygous for light-ear have light ears, tail and feet. Both coat and eyes are initially light and darken with age. As in the human disorder, homozygotes develop a platelet storage pool deficiency characterized by prolonged bleeding times (yet normal platelet counts), decreased platelet dense granule content and function, and reduced numbers of platelet dense granules. Urinary excretion of lysosomal enzymes is decreased and enzymes accumulate in the lysosomes of the kidney proximal tubules.

In mice homozygous for the retinal degeneration 1 (Pde6b^rd1) allele, developing rod cell outer segments and rod cells degenerate completely by 35 days. Cone cells also degenerate, but at much slower rate and mice retain some vision. The rd1 allele is considered a characteristic of C3H substrains and is located in close proximity to light-ear on Chr 5.

Allele

Symbol: Pde6b^rd1
Name: retinal degeneration 1
MGI accession ID: MGI:1856373
Generation method: Spontaneous
Marker symbol: Pde6b
Marker name: phosphodiesterase 6B, cGMP, rod receptor, beta polypeptide
Chromosome: 5
Strain of origin: various
Molecular note: Two mutations have been identified in rd1 mice. A murine leukimia virus (Xmv-28) insertion in reverse orientation in intron 1 is found in all mouse strains with the rd1 phenotype. Further, a nonsense mutation (C-to-A transversion) in codon 347 that results in a truncation eliminating more than half of the predicted encoded protein, including the catalytic domain, has been identified in all rd1 strains of mice. A specific degradation of mutant transcript during or after pre-mRNA splicing is suggested.
General note: The following inbred strains are known to be homozygous for Pde6b: C3H sublines, CBA/J, FVB/NJ, PL/J, SB, SJL/J, and SWR/J.

Allele

Symbol: Hps4^le
Name: light-ear
MGI accession ID: MGI:1856931
Generation method: Spontaneous
Attributes: Null/Knockout
Marker symbol: Hps4
Marker name: HPS4, biogenesis of lysosomal organelles complex 3 subunit 2
Chromosome: 5
Strain of origin: C3H/HeJ
Molecular note: The underlying mutation responsible for the phenotype in the light ear mouse was identified as a C-to-T substitution that resulted in a nonsense mutation at glutamine codon 50 (p.Q50*). The absence of protein in homozygous mutant animals was demonstrated through immunoblot analysis.