B6(C)-Kit^W-41J Gusb^mps/BrkJ

Stock number: 006564
Product name: W⁴¹ MPS VII
Research areas: Cancer Research, Dermatology Research, Developmental Biology Research, Endocrine Deficiency Research, Immunology, Inflammation and Autoimmunity Research, Metabolism Research, Mouse/Human Gene Homologs, Neurobiology Research, Reproductive Biology Research, Research Tools, Sensorineural Research

Description

These mice carry the mouse mucopolysaccharidosis VII mutation on a C57BL/6J with a dominant spotting genetic background and exhibit lysosomal storage disease. They may serve as a model for Sly disease in humans.

Detailed description

Mice homozygous for the "mps" (mucopolysaccharidosis type VII or MPS VII) mutation are devoid of expression of the lysosomal enzyme beta glucuronidase. Homozygous animals are viable, but females have a deficiency in lactation. Skeletal and connective tissue anomalies in both males and females are believed to prevent successful breeding. As this mutation is recessive, heterozygous mice are phenotypically similar to wildtype. Homozygotes exhibit short and thickened long bones (smaller than heterozygous or wildtype littermates), "pug type" appearance of the nose, hepatomegaly, splenomegaly, corneal clouding, and deafness. In appearance, homozygous Kit^W-41J mice are mostly white with black eyes and brown or grey spots. They are fertile, distinct from mice with other alleles of Kit, and have the impaired hemopoiesis causing mild, normochromic, macrocytic anemia. MPS VII mice are a model of the beta glucuronidase enzyme deficiency in humans called Sly Disease. They may be useful in developing new therapies (enzyme replacement, cell transplantation, gene therapy) broadly applicable to other lysosomal storage diseases. This strain, with combined Kit^W-41J and Gusb^mps, provides a genetically myeloablated population in which to study stem cell engraftment and reconstitution.

Development

This double mutant was generated by crossing B6.C-H2^bm1/ByBir-Gusb^mps/J (Stock No. 000256) and C57BL/6J-Kit^W-41J/J (Stock No. 000119). Progeny selected for the appropriate alleles were backcrossed to C57BL/6J-Kit^W-41J/J (Stock No. 000119) for 10 generations by Dr. Jane Barker at The Jackson Laboratory. The strain was donated to the Repository in 2007.

Allele

Symbol: Gusb^mps
Name: beta glucuronidase, mucopolysaccharidosis VII
MGI accession ID: MGI:1856041
Generation method: Spontaneous
Synonyms: asd; gus^mps; Gus-b; MPS VII
Marker symbol: Gusb
Marker name: glucuronidase, beta
Marker synonyms: Ac2-223; adipose storage deficiency; asd; BG; g; Gur; Gus; Gus-r; Gus-s; Gus-t; Gus-u; Gut; MPS7
Chromosome: 5
Strain of origin: B6.C-H2-K^bm1/By
Molecular note: A 1-bp deletion creates a frameshift mutation within exon 10, which introduces a premature stop codon at codon 497.

Allele

Symbol: Kit^W-41J
Name: dominant spotting 41 Jackson
MGI accession ID: MGI:1856244
Generation method: Spontaneous
Synonyms: Kit^W41; W⁴¹; W-41
Marker symbol: Kit
Marker name: KIT proto-oncogene receptor tyrosine kinase
Marker synonyms: belly-spot; CD117; c-KIT; Dominant white spotting; Gsfsco1; Gsfsco5; Gsfsow3; MASTC; PBT; SCFR; SCO1; SCO5; SOW3; Steel Factor Receptor; Tr-kit
Chromosome: 5
Strain of origin: C57BL/6J
Molecular note: Comparison of the coding sequence of this allele with normal c-kit indicated a G-to-A point mutation in the kinase domain at nucleotide 2519 that results in a valine to methionine substitution at amino acid 831 (p.V831M).