Description

Strain Information

Former Names STOCK Sgshmps3a/PstJ    (Changed: 24-FEB-05 ) MPS III A    (Changed: 15-DEC-04 ) Type Congenic; Mutant Strain; Additional information on Genetically Engineered Mutant Mice. Mating System Heterozygote x Heterozygote         (Female x Male) Species laboratory mouse Generation N10+1F5 (11-DEC-07)

Appearance
agouti
Related Genotype: a/a

Description
Mice homozygous for the Sgsh^mps3a 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. Sgsh^mps3a /Sgsh^mps3a 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.)

Development
The Sgsh^mps3a 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 Sgsh^mps3a mutation was detected after 4 generations and probably arose during intercrossing. The lysosomal storage disease phenotype segregated from the Mgat3^tm1Pst allele and a strain carrying the sulfamidase deficiency was developed. Thus the genetic background contains a mixture of 129SvJ, C57BL/6, SJL, and CD1 and the mutation is being backcrossed onto C57BL/6J. Mice will not be maintained from this mixed STOCK background or from specific backcross generations as the congenic is made. Consequently, future orders will be filled with mice from more advanced congenic generations.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Mucopolysaccharidosis Type IIIA - Models with phenotypic similarity to human disease where etiologies involve orthologs.1

1 Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Sgsh^mps3a/Sgsh^mps3a

        involves: 129X1/SvJ * CD-1 * C57BL/6 * SJL

• life span-post-weaning/aging
• premature death (MGI Ref ID J:72142)
  • most died between 7 and 10 months of age with a small number living to 14 months
• behavior/neurological phenotype
• circling (MGI Ref ID J:72142)
  • observed in some mice over 1 year of age
• cardiovascular system phenotype
• abnormal heart morphology (MGI Ref ID J:72142)
  • endomysium and perivascular space is often expanded by abnormal fibroblasts and macrophages
• abnormal cardiac muscle morphology (MGI Ref ID J:72142)
  • myocardiocytes ultimately undergo degenerative changes and are replaced by fibroblasts with foamy cytoplasm
• abnormal cardiac valve morphology (MGI Ref ID J:72142)
  • valvular cusps and arterial perivascular spaces are also invaded by fibroblasts
• cellular phenotype
• abnormal cell content/ morphology (MGI Ref ID J:72142)
  • vacuolated or vesiculated cells with enlarged cytoplasm in:
  • fibroblasts
  • cerebral and cerebellar neurons as well as other cells in and around the brain, dense inclusions
  • dorsal root ganglion
  • cells of the eye
  • kidney
  • cardiac tissues
• abnormal lysosome morphology (MGI Ref ID J:72142)
  • "zebra body" type storage material identifiable by EM in the brain and skeletal muscle
  • lysosomal storage is particularly prominent in the liver and spleen
• craniofacial phenotype
• abnormal calvaria morphology (MGI Ref ID J:72142)
  • thickened calvarium
• hematopoietic system phenotype
• enlarged spleen (MGI Ref ID J:72142)
• immune system phenotype
• enlarged spleen (MGI Ref ID J:72142)
• liver/biliary system phenotype
• enlarged liver (MGI Ref ID J:72142)
• muscle phenotype
• abnormal cardiac muscle morphology (MGI Ref ID J:72142)
  • myocardiocytes ultimately undergo degenerative changes and are replaced by fibroblasts with foamy cytoplasm
• renal/urinary system phenotype
• abnormal kidney morphology (MGI Ref ID J:72142)
• abnormal renal tubule morphology (MGI Ref ID J:72142)
  • microvesiculated cytoplasm in the distal convoluted tubules, podocytes, and epithelial cells lining the collecting tubules
• hydronephrosis (MGI Ref ID J:72142)
  • unilateral or bilateral hydronephrosis frequently seen
• distended urinary bladder (MGI Ref ID J:72142)
  • at death the bladder is grossly distended and contains 1-2 ml of turbid urine
  • heparan sulfate accumulation in the urine
• skeleton phenotype
• abnormal calvaria morphology (MGI Ref ID J:72142)
  • thickened calvarium
• abnormal vertebrae morphology (MGI Ref ID J:72142)
  • vertebrae become deformed
• skin/coat/nails phenotype
• abnormal hair texture (MGI Ref ID J:72142)
• disheveled coat (MGI Ref ID J:72142)
  • appeared normal at birth but developed a scruffy, ill appearance around 6-7 months of age
• vision/eye phenotype
• corneal opacity (MGI Ref ID J:72142)
  • corneal opacity develops around 7 months of age
• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:72142)
  • peripheral nerves were normal
• hearing/vestibular/ear phenotype
• circling (MGI Ref ID J:72142)
  • observed in some mice over 1 year of age

View Research Applications

Research Applications

This mouse can be used to support research in many areas including:

Sgsh^mps3a related

Cell Biology Research
Post-translational Processing

Internal/Organ Research
Bladder
Liver Defects
Spleen Defects

Mouse/Human Gene Homologs
mucopolysaccharidosis type IIIA, Sanfilippo syndrome type A

Genes & Alleles

Gene & Allele Information

Allele Symbol		Sgshmps3a
Allele Name		mucopolysaccharidosis IIIA
Allele Type		Spontaneous
Common Name(s)		MPS IIIA;
Strain of Origin		Mixed stock
Gene Symbol and Name		Sgsh, N-sulfoglucosamine sulfohydrolase (sulfamidase)
Chromosome		11
Gene Common Name(s)		4632406A19Rik; HSS; MPS3A; RIKEN cDNA 4632406A19 gene; SFMD; sulphamidase;
Molecular Note		G to A transition point mutation at position 91 of the encoded mRNA altered the corresponding amino acid from aspartic acid to asparagine at position 31 of the encoded protein. [MGI Ref ID J:72143]

Genotyping

Genotyping Information

Genotyping Protocols

Sgsh^mps3a, REST, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Bhattacharyya R; Gliddon B; Beccari T; Hopwood JJ; Stanley P. 2001. A novel missense mutation in lysosomal sulfamidase is the basis of MPS III A in a spontaneous mouse mutant. Glycobiology 11(1):99-103. [PubMed: 11181566]  [MGI Ref ID J:72143]

Bhaumik M; Muller VJ; Rozaklis T; Johnson L; Dobrenis K; Bhattacharyya R; Wurzelmann S; Finamore P; Hopwood JJ; Walkley SU; Stanley P. 1999. A mouse model for mucopolysaccharidosis type III A (Sanfilippo syndrome). Glycobiology 9(12):1389-96. [PubMed: 10561464]  [MGI Ref ID J:72142]

Additional References

Sgsh^mps3a related

Crawley AC; Gliddon BL; Auclair D; Brodie SL; Hirte C; King BM; Fuller M; Hemsley KM; Hopwood JJ. 2006. Characterization of a C57BL/6 congenic mouse strain of mucopolysaccharidosis type IIIA. Brain Res 1104(1):1-17. [PubMed: 16828069]  [MGI Ref ID J:111588]

Hemsley KM; Hopwood JJ. 2005. Development of motor deficits in a murine model of mucopolysaccharidosis type IIIA (MPS-IIIA). Behav Brain Res 158(2):191-9. [PubMed: 15698885]  [MGI Ref ID J:104452]

King B; Savas P; Fuller M; Hopwood J; Hemsley K. 2006. Validation of a heparan sulfate-derived disaccharide as a marker of accumulation in murine mucopolysaccharidosis type IIIA. Mol Genet Metab 87(2):107-12. [PubMed: 16352454]  [MGI Ref ID J:105890]

Lau AA; Crawley AC; Hopwood JJ; Hemsley KM. 2008. Open field locomotor activity and anxiety-related behaviors in mucopolysaccharidosis type IIIA mice. Behav Brain Res 191(1):130-6. [PubMed: 18453006]  [MGI Ref ID J:135197]

McIntyre C; Derrick Roberts AL; Ranieri E; Clements PR; Byers S; Anson DS. 2008. Lentiviral-mediated gene therapy for murine mucopolysaccharidosis type IIIA. Mol Genet Metab 93(4):411-8. [PubMed: 18248829]  [MGI Ref ID J:134228]

Settembre C; Fraldi A; Jahreiss L; Spampanato C; Venturi C; Medina D; de Pablo R; Tacchetti C; Rubinsztein DC; Ballabio A. 2008. A block of autophagy in lysosomal storage disorders. Hum Mol Genet 17(1):119-29. [PubMed: 17913701]  [MGI Ref ID J:132024]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX11

Colony Maintenance

Mating System	Heterozygote x Heterozygote         (Female x Male)
Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Live. A collection of over 1000 strains maintained as live colonies. Individual colonies are sized to meet current customer demand. Delivery for orders of 10 mice or less ranges on average from one to eight weeks; mice are generally shipped between four to six weeks of age with a maximum shipping age of ~nine weeks. Colony sizes do not generally support stringent age specifications for large volumes of mice; however custom orders and larger quantities of mice are easily arranged. Estimated ship dates for all orders provided within 48 hours of order placement.

Supply Notes

Usually shipped between four and eight weeks of age. This strain is included in the Mouse Mutant Resource collection. Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	000664 C57BL/6J
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX^® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX^® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX^® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.

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fax:	207-288-6655

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