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 N1F5p+N1p (20-NOV-05) Generation Definitions   Donating Investigator Richard L Proia,   National Institutes of Health

Appearance
white-bellied agouti
Related Genotype: A^w/?

black
Related Genotype: a/a

Description
Mice homozygous for the Hexb^tm1Rlp targeted mutation develop motor defects beginning at about 3 months of age. The defects progressively worsen and homozygous mice die by 4.5 months of age. Mice display gangliosidosis; mice abnormally accumulate GM2 and GA2 ganglioside and serve as a model of Sandhoff disease.

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Sandhoff Disease

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

Hexb^tm1Rlp/Hexb^tm1Rlp

        involves: 129S4/SvJae * C57BL/6

• mortality/aging
• premature death
  • died around 120 to 150 days of age   (MGI Ref ID J:53080)
  • average life span of 127 days   (MGI Ref ID J:190450)
• behavior/neurological phenotype
• abnormal motor capabilities/coordination/movement
  • beginning at 3 months and progressing with age   (MGI Ref ID J:29268)
• • abnormal gait
    • spastic movements of hind limbs starting around 5 months   (MGI Ref ID J:29268)
    • near lack of hind limb movement by 5 months and fore limbs also afflicted   (MGI Ref ID J:29268)
  • bradykinesia
    • by 4 - 5 months of age   (MGI Ref ID J:190450)
  • impaired coordination
    • performance in a rotarod test is impaired at 9 weeks and declines very rapidly after 11 weeks of age   (MGI Ref ID J:29268)
    • at 16 weeks of age, homozygous mice are unable to stay on a rotarod   (MGI Ref ID J:29268)
  • impaired righting response
    • progressive loss of righting response with age   (MGI Ref ID J:53080)
  • tremors
    • by 4 - 5 months of age   (MGI Ref ID J:190450)
• nervous system phenotype
• abnormal neuron morphology
  • neuronal storage vacuoles (PAS positive) found throughout the central nervous system   (MGI Ref ID J:29268)
  • vacuoles very abundant in anterior horn motor neurons of the spinal cord   (MGI Ref ID J:29268)
  • PAS positive granules also found in neuropil and dendrites   (MGI Ref ID J:29268)
  • no granules found in cerebral and cerebellar white matter, nerve fiber tracts, spinal roots or optic nerves   (MGI Ref ID J:29268)
• muscle phenotype
• muscular atrophy
  • at 5 months of age   (MGI Ref ID J:29268)
• liver/biliary system phenotype
• abnormal liver morphology
  • storage vacuoles found in cells in hepatic sinusoids   (MGI Ref ID J:29268)
• • abnormal hepatocyte morphology
    • PAS positive storage vacuoles found   (MGI Ref ID J:29268)
• renal/urinary system phenotype
• abnormal proximal convoluted tubule morphology
  • storage vacuoles found in epithelial cells of the proximal tubules   (MGI Ref ID J:29268)
• growth/size phenotype
• weight loss
  • by 4 - 5 months of age   (MGI Ref ID J:190450)

View Research Applications

Research Applications

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

Hexb^tm1Rlp related

Metabolism Research

Neurobiology Research
Metabolic Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Hexbtm1Rlp
Allele Name		targeted mutation 1, Richard L Proia
Allele Type		Targeted (knock-out)
Common Name(s)		Hexb-; Sandhoff hexb-;
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		Hexb, hexosaminidase B
Chromosome		13
Gene Common Name(s)		ENC-1AS;
Molecular Note		A neomycin resistance cassette was inserted into and disrupted exon 13 of the gene. This mutation resulted in the production of no detectable functional protein. [MGI Ref ID J:29268]

Genotyping

Genotyping Information

Genotyping Protocols

Hexb^tm1Rlp, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Sango K; Yamanaka S; Hoffmann A; Okuda Y; Grinberg A; Westphal H; McDonald MP; Crawley JN; Sandhoff K; Suzuki K; Proia RL.. 1995. Mouse models of Tay-Sachs and Sandhoff diseases differ in neurologic phenotype and ganglioside metabolism. Nat Genet 11(2):170-6. [PubMed: 7550345]  [MGI Ref ID J:29268]

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]

Hexb^tm1Rlp related

Boland B; Smith DA; Mooney D; Jung SS; Walsh DM; Platt FM. 2010. Macroautophagy is not directly involved in the metabolism of amyloid precursor protein. J Biol Chem 285(48):37415-26. [PubMed: 20864542]  [MGI Ref ID J:167334]

Buccoliero R; Bodennec J; Van Echten-Deckert G; Sandhoff K; Futerman AH. 2004. Phospholipid synthesis is decreased in neuronal tissue in a mouse model of Sandhoff disease. J Neurochem 90(1):80-8. [PubMed: 15198669]  [MGI Ref ID J:91444]

De Santo C; Salio M; Masri SH; Lee LY; Dong T; Speak AO; Porubsky S; Booth S; Veerapen N; Besra GS; Grone HJ; Platt FM; Zambon M; Cerundolo V. 2008. Invariant NKT cells reduce the immunosuppressive activity of influenza A virus-induced myeloid-derived suppressor cells in mice and humans. J Clin Invest 118(12):4036-48. [PubMed: 19033672]  [MGI Ref ID J:144728]

Denny CA; Alroy J; Pawlyk BS; Sandberg MA; d'Azzo A; Seyfried TN. 2007. Neurochemical, morphological, and neurophysiological abnormalities in retinas of Sandhoff and GM1 gangliosidosis mice. J Neurochem 101(5):1294-302. [PubMed: 17442056]  [MGI Ref ID J:122595]

Denny CA; Heinecke KA; Kim YP; Baek RC; Loh KS; Butters TD; Bronson RT; Platt FM; Seyfried TN. 2010. Restricted ketogenic diet enhances the therapeutic action of N-butyldeoxynojirimycin towards brain GM2 accumulation in adult Sandhoff disease mice. J Neurochem 113(6):1525-35. [PubMed: 20374428]  [MGI Ref ID J:163568]

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]

Gulinello M; Chen F; Dobrenis K. 2008. Early deficits in motor coordination and cognitive dysfunction in a mouse model of the neurodegenerative lysosomal storage disorder, Sandhoff disease. Behav Brain Res 193(2):315-9. [PubMed: 18611415]  [MGI Ref ID J:139219]

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; Butters TD; Cortina-Borja M; Hunnam V; Proia RL; Perry VH; Dwek RA; Platt FM. 1999. Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin. Proc Natl Acad Sci U S A 96(11):6388-93. [PubMed: 10339597]  [MGI Ref ID J:55198]

Keilani S; Lun Y; Stevens AC; Williams HN; Sjoberg ER; Khanna R; Valenzano KJ; Checler F; Buxbaum JD; Yanagisawa K; Lockhart DJ; Wustman BA; Gandy S. 2012. Lysosomal dysfunction in a mouse model of Sandhoff disease leads to accumulation of ganglioside-bound amyloid-beta peptide. J Neurosci 32(15):5223-36. [PubMed: 22496568]  [MGI Ref ID J:184450]

Liu Y; Wada R; Kawai H; Sango K; Deng C; Tai T; McDonald MP; Araujo K; Crawley JN; Bierfreund U; Sandhoff K; Suzuki K; Proia RL. 1999. A genetic model of substrate deprivation therapy for a glycosphingolipid storage disorder [see comments] J Clin Invest 103(4):497-505. [PubMed: 10021458]  [MGI Ref ID J:53080]

Mallevaey T; Zanetta JP; Faveeuw C; Fontaine J; Maes E; Platt F; Capron M; de-Moraes ML; Trottein F. 2006. Activation of invariant NKT cells by the helminth parasite schistosoma mansoni. J Immunol 176(4):2476-85. [PubMed: 16456008]  [MGI Ref ID J:129188]

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]

Norflus F; Tifft CJ; McDonald MP; Goldstein G; Crawley JN; Hoffmann A; Sandhoff K; Suzuki K; Proia RL. 1998. Bone marrow transplantation prolongs life span and ameliorates neurologic manifestations in Sandhoff disease mice. J Clin Invest 101(9):1881-8. [PubMed: 9576752]  [MGI Ref ID J:47677]

Pelled D; Lloyd-Evans E; Riebeling C; Jeyakumar M; Platt FM; Futerman AH. 2003. Inhibition of calcium uptake via the sarco/endoplasmic reticulum Ca2+-ATPase in a mouse model of Sandhoff disease and prevention by treatment with N-butyldeoxynojirimycin. J Biol Chem 278(32):29496-501. [PubMed: 12756243]  [MGI Ref ID J:84955]

Pelled D; Riebeling C; van Echten-Deckert G; Sandhoff K; Futerman AH. 2003. Reduced rates of axonal and dendritic growth in embryonic hippocampal neurones cultured from a mouse model of Sandhoff disease. Neuropathol Appl Neurobiol 29(4):341-9. [PubMed: 12887594]  [MGI Ref ID J:103900]

Plati T; Visigalli I; Capotondo A; Buono M; Naldini L; Cosma MP; Biffi A. 2009. Development and maturation of invariant NKT cells in the presence of lysosomal engulfment. Eur J Immunol 39(10):2748-54. [PubMed: 19637231]  [MGI Ref ID J:153255]

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]

Sango K; Takano M; Ajiki K; Tokashiki A; Arai N; Kawano H; Horie H; Yamanaka S. 2005. Impaired neurite outgrowth in the retina of a murine model of Sandhoff disease. Invest Ophthalmol Vis Sci 46(9):3420-5. [PubMed: 16123447]  [MGI Ref ID J:101337]

Sango K; Yamanaka S; Ajiki K; Tokashiki A; Watabe K. 2002. Lysosomal storage results in impaired survival but normal neurite outgrowth in dorsal root ganglion neurones from a mouse model of Sandhoff disease. Neuropathol Appl Neurobiol 28(1):23-34. [PubMed: 11849560]  [MGI Ref ID J:103802]

Sargeant TJ; Drage DJ; Wang S; Apostolakis AA; Cox TM; Cachon-Gonzalez MB. 2012. Characterization of inducible models of Tay-Sachs and related disease. PLoS Genet 8(9):e1002943. [PubMed: 23028353]  [MGI Ref ID J:190450]

Sargeant TJ; Wang S; Bradley J; Smith NJ; Raha AA; McNair R; Ziegler RJ; Cheng SH; Cox TM; Cachon-Gonzalez MB. 2011. Adeno-associated virus-mediated expression of {beta}-hexosaminidase prevents neuronal loss in the Sandhoff mouse brain. Hum Mol Genet 20(22):4371-80. [PubMed: 21852247]  [MGI Ref ID J:176890]

Suzuki K; Iseki E; Katsuse O; Yamaguchi A; Katsuyama K; Aoki I; Yamanaka S; Kosaka K. 2003. Neuronal accumulation of alpha- and beta-synucleins in the brain of a GM2 gangliosidosis mouse model. Neuroreport 14(4):551-4. [PubMed: 12657883]  [MGI Ref ID J:89803]

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]

Tsuji D; Kuroki A; Ishibashi Y; Itakura T; Kuwahara J; Yamanaka S; Itoh K. 2005. Specific induction of macrophage inflammatory protein 1-alpha in glial cells of Sandhoff disease model mice associated with accumulation of N-acetylhexosaminyl glycoconjugates. J Neurochem 92(6):1497-507. [PubMed: 15748167]  [MGI Ref ID J:96874]

Vitner EB; Dekel H; Zigdon H; Shachar T; Farfel-Becker T; Eilam R; Karlsson S; Futerman AH. 2010. Altered expression and distribution of cathepsins in neuronopathic forms of Gaucher disease and in other sphingolipidoses. Hum Mol Genet 19(18):3583-90. [PubMed: 20616152]  [MGI Ref ID J:163168]

Wada R; Tifft CJ; Proia RL. 2000. Microglial activation precedes acute neurodegeneration in sandhoff disease and is suppressed by bone marrow transplantation Proc Natl Acad Sci U S A 97(20):10954-9. [PubMed: 11005868]  [MGI Ref ID J:64739]

Wu YP; Mizugishi K; Bektas M; Sandhoff R; Proia RL. 2008. Sphingosine kinase 1/S1P receptor signaling axis controls glial proliferation in mice with Sandhoff disease. Hum Mol Genet 17(15):2257-64. [PubMed: 18424450]  [MGI Ref ID J:137634]

Wu YP; Proia RL. 2004. Deletion of macrophage-inflammatory protein 1 alpha retards neurodegeneration in Sandhoff disease mice. Proc Natl Acad Sci U S A 101(22):8425-30. [PubMed: 15155903]  [MGI Ref ID J:90687]

Yamaguchi A; Katsuyama K; Nagahama K; Takai T; Aoki I; Yamanaka S. 2004. Possible role of autoantibodies in the pathophysiology of GM2 gangliosidoses. J Clin Invest 113(2):200-8. [PubMed: 14722612]  [MGI Ref ID J:87617]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	Wild-type from the colony
	101045 B6129SF2/J	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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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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