Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation +N1 Generation Definitions   Donating Investigator Richard Proia,   National Institutes of Health

Description
Mice homozygous for the Hexa^tm1Rlp targeted mutation are viable and fertile. GM2 ganglioside accumulates in the central nervous system of homozygous mice and the neuropathology is similar to that of Tay-Sachs patients with the exception that not all neurons are affected in the mouse as in human beings. No neuronal storage was found in the cerebellum, the anterior horn of the spinal cord or the spinal ganglia. Only minor storage was present in the posterior horn of the spinal cord. There are no abnormal neurologic signs in homozygous mice by 5 months of age.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

Tay-Sachs Disease; TSD - 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 provided by MGI

      assigned by genotype

Hexa^tm1Rlp/Hexa^tm1Rlp

        involves: 129S4/SvJae * C57BL/6

• nervous system phenotype
• abnormal brain morphology
  • accumulation of G_M2 gangliosides levels reach 15% of total gangliosides   (MGI Ref ID J:21008)
  • levels reach 15% of total gangliosides   (MGI Ref ID J:21008)
• abnormal neuron morphology
  • number of storage neurons with membranous cytoplasmic bodies increases with age   (MGI Ref ID J:21008)
  • distribution of storage neurons found in cerebral cortex, piriform and entorhinal cortices, CA3, amygdala, mammillary bodies, septal nuclei, and nuclei in the hypothalamus   (MGI Ref ID J:21008)

View Research Applications

Research Applications

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

Hexa^tm1Rlp related

Metabolism Research

Mouse/Human Gene Homologs
GM2-gangliosidosis type I, Tay-Sachs disease

Neurobiology Research
Metabolic Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Hexatm1Rlp
Allele Name		targeted mutation 1, Richard L Proia
Allele Type		Targeted (knock-out)
Common Name(s)		Hexa-; Tay-Sachs; Tay-Sachs hexa-;
Mutation Made By		Richard Proia,   National Institutes of Health
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Hexa, hexosaminidase A
Chromosome		9
Gene Common Name(s)		Hex-1; TSD;
Molecular Note		A neomycin resistance cassette was inserted into and disrupted exon 8 of the gene. Northern blots of liver homogenates from homozygous mutant mice showed no detectable transcript. This mutation resulted in the production of no detectable functional protein. [MGI Ref ID J:21008]

Genotyping

Genotyping Information

Genotyping Protocols

Hexa^tm1Rlp, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Yamanaka S; Johnson MD; Grinberg A; Westphal H; Crawley JN; Taniike M; Suzuki K; Proia RL. 1994. Targeted disruption of the Hexa gene results in mice with biochemical and pathologic features of Tay-Sachs disease. Proc Natl Acad Sci U S A 91(21):9975-9. [PubMed: 7937929]  [MGI Ref ID J:21008]

Additional References

Sango K; McDonald MP; Crawley JN; Mack ML; Tifft CJ; Skop E; Starr CM; Hoffmann A; Sandhoff K; Suzuki K; Proia RL. 1996. Mice lacking both subunits of lysosomal beta-hexosaminidase display gangliosidosis and mucopolysaccharidosis. Nat Genet 14(3):348-52. [PubMed: 8896570]  [MGI Ref ID J:36305]

Hexa^tm1Rlp related

Gadola SD; Silk JD; Jeans A; Illarionov PA; Salio M; Besra GS; Dwek R; Butters TD; Platt FM; Cerundolo V. 2006. Impaired selection of invariant natural killer T cells in diverse mouse models of glycosphingolipid lysosomal storage diseases. J Exp Med 203(10):2293-303. [PubMed: 16982810]  [MGI Ref ID J:124639]

Hepbildikler ST; Sandhoff R; Kolzer M; Proia RL; Sandhoff K. 2002. Physiological substrates for human lysosomal beta -hexosaminidase S. J Biol Chem 277(4):2562-72. [PubMed: 11707436]  [MGI Ref ID J:124832]

Jeyakumar M; Smith D; Eliott-Smith E; Cortina-Borja M; Reinkensmeier G; Butters TD; Lemm T; Sandhoff K; Perry VH; Dwek RA; Platt FM. 2002. An inducible mouse model of late onset Tay-Sachs disease. Neurobiol Dis 10(3):201-10. [PubMed: 12270683]  [MGI Ref ID J:125673]

Martino S; di Girolamo I; Cavazzin C; Tiribuzi R; Galli R; Rivaroli A; Valsecchi M; Sandhoff K; Sonnino S; Vescovi A; Gritti A; Orlacchio A. 2009. Neural precursor cell cultures from GM2 gangliosidosis animal models recapitulate the biochemical and molecular hallmarks of the brain pathology. J Neurochem 109(1):135-47. [PubMed: 19166507]  [MGI Ref ID J:149170]

Platt FM; Neises GR; Reinkensmeier G; Townsend MJ; Perry VH; Proia RL ; Winchester B ; Dwek RA ; Butters TD. 1997. Prevention of lysosomal storage in Tay-Sachs mice treated with N-butyldeoxynojirimycin. Science 276(5311):428-31. [PubMed: 9103204]  [MGI Ref ID J:39569]

Sango K; McDonald MP; Crawley JN; Mack ML; Tifft CJ; Skop E; Starr CM; Hoffmann A; Sandhoff K; Suzuki K; Proia RL. 1996. Mice lacking both subunits of lysosomal beta-hexosaminidase display gangliosidosis and mucopolysaccharidosis. Nat Genet 14(3):348-52. [PubMed: 8896570]  [MGI Ref ID J:36305]

Suzuki K; Sango K; Proia RL; Langaman C. 1997. Mice deficient in all forms of lysosomal beta-hexosaminidase show mucopolysaccharidosis-like pathology. J Neuropathol Exp Neurol 56(6):693-703. [PubMed: 9184660]  [MGI Ref ID J:41920]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, RG10/RG30.

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

Pricing, Supply Level & Notes, Controls

General Supply Notes

• This strain is included in the Induced Mutant Resource Colony collection.
• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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