These mice carry a spontaneous mutation at the Sgsh locus characterized by scruffy coat, hunched posture, and reduced activity, and corneal opacity as a result of extensive lysosomal accumulation of heparin sulfate most prominently in neuronal tissue and liver and, to a lesser degree, in the spleen.Read More +
Mice homozygous for the Sgshmps3a mutation have only 3-4% of the wild type level of sulfamidase activity. This results in extensive lysosomal accumulation of heparin sulfate most prominently in neuronal tissue and liver and, to a lesser degree, in the spleen. GM2 ganglioside accumulation is also found. The outward phenotype of scruffy coat, hunched posture, and reduced activity is usually seen by 6 to 7 months of age. Corneal opacity is also found at approximately 7 months of age. Death occurs between 7 and 10 months of age, on average, and autopsy reveals brain lesions, hepatosplenomegaly and a distended bladder containing turbid urine. The homozygotes have thicker skullcaps, vertebral deformation, thickening of the urinary bladder wall, and bladder blockage that leads to severe bladder distention as they age. Sgshmps3a /Sgshmps3a mice provide a model for the human disease mucopolysaccharidosis 3A (MPSIIIA), also known as Sanfilippo syndrome type A. The electrophoresis banding pattern of glycosaminoglycans from the brain and urine of homozygous mice is similar to the abnormal pattern found in samples from human MPSIIIA patients. The human disease symptoms include severe central nervous system degeneration, claw hand, and visceromegaly, with death occurring in the second or third decade of life. Please see OMIM for more details. (Bhaumik et al., 1999; Bhattacharyya et al., 2001.)
The Sgshmps3a mutation arose in a colony developed from a chimera formed by injecting WW6 embryonic stem cells with a targetted mutation in the Mgat3 gene into C57BL/6 blastocysts. The ES cell clone did not carry the mutation. A female chimera was subsequently crossed with a CD1 male and Mgat3 heterozygotes were intercrossed. The Sgshmps3a mutation was detected after 4 generations and probably arose during intercrossing. The lysosomal storage disease phenotype segregated from the Mgat3tm1Pst allele and a strain carrying the sulfamidase deficiency was developed. Thus the genetic background was originally a mixture of 129SvJ, C57BL/6, SJL, and CD1. Thereafter, the mutation was backcrossed onto C57BL/6J. By 2017, the cryopreserved materials for Stock No. 003780 are backcrossed onto C57BL/6J for a total of 14 or more generations.
|Allele Name||mucopolysaccharidosis IIIA|
|Allele Synonym(s)||MPS IIIA|
|Gene Symbol and Name||Sgsh, N-sulfoglucosamine sulfohydrolase (sulfamidase)|
|Strain of Origin||Mixed stock|
|Molecular Note||A G-to-A transition point mutation at coding nucleotide 91 of the encoded mRNA (c.91G>A) altered the corresponding amino acid from aspartic acid to asparagine at position 31 of the encoded protein (p.D31N).|
Homozygous mice die between 7-10 months of age (see strain phenotype description). When maintaining a live colony, heterozygous mice may be bred together, to wildtype mice from the colony or to C57BL/6J inbred mice (Stock No. 000664).
When using the B6.Cg-Sgshmps3a/PstJ mouse strain in a publication, please cite the originating article(s) and include JAX stock #003780 in your Materials and Methods section.
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