Description

Strain Information

Type Congenic; Mutant Strain; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6J Donor Strain CE/J Generation F69+2N8F1+N1

Appearance
black, tremors
Related Genotype: a/a Galc^twi/Galc^twi

black, unaffected
Related Genotype: a/a +/?

Description
The twitcher mouse is a neurological leukodystrophy mutant first observed in 1976 at The Jackson Laboratory. Initially characterized on a mixed C57BL/6J and CE/J background, clinical symptoms were first observed by day 30 and homozygotes did not survive beyond three months of age. (Duchen LW, et. al., 1980) Subsequent backcrosses to C57BL/6J and the generation of a full congenic (> 10 backcrosses) reduced the onset of symptoms to approximately 21 days with death by 40 days. Head tremors and decreased body weight are initial clinical indicators and mice are generally less active than unaffected littermates. Muscle weakness in the hindlimbs is a promiment feature and clinically, the health of the mutants progressively declines until death. There is a significant lack of myelin in the twitcher CNS, along with astrocytic gliosis. The nerves in the PNS are also demyelinated. The mutant CNS and PNS contain multinucleated, periodic acid-Schiff-positive globoid cells. Electron microscopic analysis shows these cells contain paracrystalline inclusions and twisted tubules.

Galactosylceramidase (GALC) is the enzyme responsible for the initial step of galactosylceramide (or galactocerebroside) degradation. Galactocerebroside is one of the most abundant and unique lipid constituents of the myelin sheath and the twitcher mouse is a useful mutant in which to study myelina tion and myelin metabolism. This substrate of the enzyme GALC, however, does not accumulate in tissues of affected mice (or humans). The pathol ogies are believed to result from the abnormal accumulation of the cytotoxic metabolite galactosylsphingosine (psychosine), another substrate of GALC that inhibits protein kinase C, that causes myelin-forming cells of the CNS and PNS to dysfunction and undergo apoptosis. Levels of myelin protein mRNAs are normal through postnatal day 20 but decline after day 25, corresponding to the observed pathological demyelinating changes. The data indicate that specific gene expression during myelination appears normal initially. Astrogliosis in the CNS is initiated prior to the appearance of myelin pathologies (as early as postnatal 15) and GFAP mRNA is highly upregulated after day 20, presumably as a response to demyelination. Cytokines are believed to play a major role in the inflammatory responses associated with the disease course. TNF-alpha and IL-6 in the CNS appear to be induced by the pathological condition; reactive astrocytes and microglia contribute to the pathogenic course in the CNS of these mutants.(Taniike et al., 1998; Kobayashi et al., 1980; Suzuki and Suzuki, 1995; LeVine and Brown, 1997; Matsushima et al., 1994).

Development
The twitcher mouse contains a recessive mutation (Galc^twi) that spontaneously arose at The Jackson Laboratory in 1976 in the CE/J strain. The mutant allele has been put onto the C57BL/6J strain by means of ovarian transplantation. The female host carrying the homozygous mutation is crossed to a C57BL/6J male and the colony is maintained by intercrossing the obligate heterozygote offspring.

Control Information

	Control
	Untyped from the colony
Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Galc

000978	B10.A/(5R)SgSn-Galctwi-2J/J
003613	BXD32/TyJ-Galctwi-5J/J

View Strains carrying other alleles of Galc     (2 strains)

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms

Krabbe Disease - 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

Galc^twi/Galc^twi

        B6.CE-Galc^twi/J

• life span-post-weaning/aging
• premature death (MGI Ref ID J:108359)
  • lifespan of mutants is 45.5 days; death is result of peripheral and cranial nerve palsy
• homeostasis/metabolism phenotype
• abnormal enzyme/coenzyme activity (MGI Ref ID J:108359)
  • levels of Ptgds2 activity are 3-fold higher in the cerebrum and 5-fold higher in the cerebellum of mutants compared to wild-type
• behavior/neurological phenotype
• ataxia (MGI Ref ID J:108359)
• impaired righting response (MGI Ref ID J:108359)
  • mutants have poorer righting response compared to wild-type or Ptgds2/Galc double mutants
• tremors (MGI Ref ID J:108359)
  • mutants barely stagger with strong intentional tremor
• nervous system phenotype
• abnormal astrocyte morphology (MGI Ref ID J:108359)
  • there are hypertrophied astrocytes with large soma and thick-branched processes in mutant brains
• abnormal microglial cell morphology (MGI Ref ID J:108359)
  • microglia in mutant brains have increased levels of Ptgds2 protein and have irregular thick processes in the region of demyelination
• demyelination (MGI Ref ID J:108359)
  • 39 day-old mutant brains exhibit demyelination; demyelination appears to be restricted to the CNS
• hematopoietic system phenotype
• abnormal microglial cell morphology (MGI Ref ID J:108359)
  • microglia in mutant brains have increased levels of Ptgds2 protein and have irregular thick processes in the region of demyelination
• immune system phenotype
• abnormal microglial cell morphology (MGI Ref ID J:108359)
  • microglia in mutant brains have increased levels of Ptgds2 protein and have irregular thick processes in the region of demyelination

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

Galc^twi/Galc^twi

        CE/J

• nervous system phenotype
• CNS inflammation (MGI Ref ID J:78223)
  • mice show greater macrophage infiltration than Psap^tm1Suz mice
• demyelination (MGI Ref ID J:78223)
  • mice show more severe demyelination than Psap^tm1Suz mice
• immune system phenotype
• CNS inflammation (MGI Ref ID J:78223)
  • mice show greater macrophage infiltration than Psap^tm1Suz mice
• homeostasis/metabolism phenotype
• abnormal lipid level (MGI Ref ID J:78223)
  • 45-day old mice have a much greater accumulation of galactosylceramide in kidney is greater than in 4-month old Psap-deficient mice
  • at 40 days, brain levels of psychosine (galactosylsphingosine) are much higher than in wild-type controls or Psap-deficient mice (223 pmol/mg vs 60 or 32 pmol/mg)

View Research Applications

Research Applications

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

Galc^twi related

Mouse/Human Gene Homologs
globoid cell leukodystrophy (Krabbe disease)

Neurobiology Research
Myelination Defects
Tremor Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Galctwi
Allele Name		twitcher
Allele Type		Spontaneous
Common Name(s)		galc-; twi;
Strain of Origin		CE/J
Gene Symbol and Name		Galc, galactosylceramidase
Chromosome		12
Gene Common Name(s)		2310068B06Rik; A930008M05Rik; AW212969; AW413532; Gacy; RIKEN cDNA 2310068B06 gene; RIKEN cDNA A930008M05 gene; expressed sequence AW212969; expressed sequence AW413532; galactocerebrosidase; twi; twitcher;
General Note		This mutation arose spontaneously in the CE/J inbred strain at The Jackson Laboratory (J:13867). Homozygotes can be recognized at about 3 weeks of age by a generalized tremor. Progressive weakness and wasting follow and death occurs by about 3 months (J:6390).The principal pathological changes are degeneration of myelin sheaths in both the central and peripheral nervous systems, presence of multinucleated macrophages (globoid cells) containing a variety of inclusions in which there are crystalline and multi-angular structures and twisted tubules (J:6390), and endoneurial edema (J:7115). These abnormalities closely resemble those of human globoid cell leukodystrophy (Krabbe's disease) (J:6390).In the brain and liver of twitcher homozygotes, there is aprofound deficiency of galactosylceramidase and lactosylceramidase activity. Heterozygotes have intermediate levels of both enzymes. Twitcher is thus a model enzymatically, as well as morphologically and clinically, of Krabbe's disease (J:6423). Human Krabbe's disease cell/mouse twitcher cell hybrids show no complementation for the missing enzyme (J:35073).In the central nervous system oligodendrocytes (J:31433), and in the peripheral nervous system Schwann cells (J:6477), form myelin. Dysfunction and degeneration of these cells in twitcher mice leads to the loss of myelination characteristic of the gene defect. The defect was shown to be intrinsic to the Schwann cells in peripheral nerve by means of nerve-grafting experiments (J:6477). When sciatic nerves from affected mice were grafted into trembler (Pmp22/+) mice, which have defective Schwann cells, 1 to 4 months after grafting they showed normal myelin, no globoid cells, and very little endoneurial edema (J:6749). Grafting to normal hosts also results in increased galactosylceramidase activity, presumably due to enzyme replacement in the mutant Schwann cells (J:7223). Proliferative capacity of Schwann cells was shown to be reduced in Galctwi/Galctwi homozygotes, even before demyelination becomes evident (J:3584).Transplantation of normal hematopoietic cells into twitcher mice gradually repairs the demyelination of the peripheral nerves, probably by enzyme transfer from normal macrophages (J:7576). When wild-type fetal liver cells, as a source of normal hematopoietic tissue, and fetal brain cells, as a source of normal oligodendrocytes, are transplanted together into twitcher mice, the increase in survival time is greater than with hematopoietic cells alone, and transplanted oligodendrocytes disseminate throughout the central nervous system (J:1327). Native oligodendrocytes are capable of proliferating within the twitcher spinal cord, but total numbers decline because degeneration exceeds proliferation (J:23073).In spite of the deficiency of enzyme in affected mice and in patients with Krabbe's disease, there is no accumulation of the normal substrate, galactosylceramide, in the nervous system. However, in twitcher mice, beginning at 7 days old, there is a rapid and progressive accumulation of atoxic metabolite, psychosine (galactosylsphingosine), which is also a substrate for galactosylceramidase. No psychosine was detected in either homozygous normal or heterozygous mice. The accumulation of psychosine is thought to be responsible for death of myelin-forming cells and demyelination in affected mice and probably also in patients with Krabbe's disease (J:7427).Globoid cells characteristic of neural tissue in twitcher mice are microglia/macrophages engorged with cell debris and galactosylceramide (J:3948). A subset of these cells express class II major histocompatibility complex molecules (H2-A and H2-E) (J:2124). This expression may be a local reaction to degenerating tissue components; on the other hand, it may represent pathogenic involvement of immunological responses in cell degeneration (J:15111). A reduction in central nervous system demyelination, infiltration of microglia or macrophages, and twitching in twitcher mice with a null mutation for H2-Ab1 suggests a possible causative role (J:19914).In the kidneys of twitcher mice, in contrast to the nervous system, there is a large increase of galactosylceramide (50x normal), with a smaller increase in liver and lung (J:7311). This is accompanied by presence in the loop of Henle of the kidneys of large numbers of inclusions of the type found in the globoid cells of the nervous system (J:7313).
Molecular Note		Sequence analysis comparisons of cDNA from livers of mice homozygous for this allele and +/+ mice showed a G to A transition at codon 339. Northern analysis showed absence of the most abundant mRNA of mouse galactocerebrosidase in mice homozygous for this allele. [MGI Ref ID J:31433]

Genotyping

Genotyping Information

This strain will not have a genotyping protocol or one is not currently available.

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

D'Eustachio P; Clarke V. 1993. Localization of the twitcher (twi) mutation on mouse chromosome 12. Mamm Genome 4(11):684-6. [PubMed: 8281019]  [MGI Ref ID J:15634]

Duchen LW; Eicher EM; Jacobs JM; Scaravilli F; Teixeira F. 1980. Hereditary leucodystrophy in the mouse: the new mutant twitcher. Brain 103(3):695-710. [PubMed: 7417782]  [MGI Ref ID J:6390]

Kobayashi T; Yamanaka T; Jacobs JM; Teixeira F; Suzuki K. 1980. The Twitcher mouse: an enzymatically authentic model of human globoid cell leukodystrophy (Krabbe disease). Brain Res 202(2):479-83. [PubMed: 7437911]  [MGI Ref ID J:6423]

LeVine SM; Brown DC. 1997. IL-6 and TNFalpha expression in brains of twitcher, quaking and normal mice. J Neuroimmunol 73(1-2):47-56. [PubMed: 9058758]  [MGI Ref ID J:40116]

Matsushima GK; Taniike M; Glimcher LH; Grusby MJ; Frelinger JA; Suzuki K; Ting JP. 1994. Absence of MHC class II molecules reduces CNS demyelination, microglial/macrophage infiltration, and twitching in murine globoid cell leukodystrophy. Cell 78(4):645-56. [PubMed: 8069913]  [MGI Ref ID J:19914]

Suzuki K; Suzuki K. 1995. The twitcher mouse: a model for Krabbe disease and for experimental therapies. Brain Pathol 5(3):249-58. [PubMed: 8520724]  [MGI Ref ID J:29140]

Taniike M; Mohri I; Eguchi N; Beuckmann CT; Suzuki K; Urade Y. 2002. Perineuronal oligodendrocytes protect against neuronal apoptosis through the production of lipocalin-type prostaglandin D synthase in a genetic demyelinating model. J Neurosci 22(12):4885-96. [PubMed: 12077186]  [MGI Ref ID J:77531]

Wu YP; McMahon E; Kraine MR; Tisch R; Meyers A; Frelinger J; Matsushima GK; Suzuki K. 2000. Distribution and characterization of GFP(+) donor hematogenous cells in Twitcher mice after bone marrow transplantation. Am J Pathol 156(6):1849-54. [PubMed: 10854208]  [MGI Ref ID J:62662]

Galc^twi related

Biswas S; Biesiada H; Williams TD; LeVine SM. 2002. Delayed clinical and pathological signs in twitcher (globoid cell leukodystrophy) mice on a C57BL/6 x CAST/Ei background. Neurobiol Dis 10(3):344-57. [PubMed: 12270695]  [MGI Ref ID J:126892]

Cho SK; Gao N; Pearce DA; Lehrman MA; Hofmann SL. 2005. Characterization of lipid-linked oligosaccharide accumulation in mouse models of Batten disease. Glycobiology 15(6):637-48. [PubMed: 15647513]  [MGI Ref ID J:112499]

Contreras MA; Haq E; Uto T; Singh I; Singh AK. 2008. Psychosine-induced alterations in peroxisomes of twitcher mouse liver. Arch Biochem Biophys 477(2):211-8. [PubMed: 18602885]  [MGI Ref ID J:141880]

Costantino-Ceccarini E; Luddi A; Volterrani M; Strazza M; Rafi MA ; Wenger DA. 1999. Transduction of cultured oligodendrocytes from normal and twitcher mice by a retroviral vector containing human galactocerebrosidase (GALC) cDNA. Neurochem Res 24(2):287-93. [PubMed: 9972877]  [MGI Ref ID J:52953]

Duchen LW. 1981. A new neurological mutant "twitcher" (twi) Mouse News Lett 61:47.  [MGI Ref ID J:13867]

Duchen LW; Eicher EM; Jacobs JM; Scaravilli F; Teixeira F. 1980. Hereditary leucodystrophy in the mouse: the new mutant twitcher. Brain 103(3):695-710. [PubMed: 7417782]  [MGI Ref ID J:6390]

Ezoe T; Vanier MT; Oya Y; Popko B; Tohyama J; Matsuda J; Suzuki K; Suzuki K. 2000. Biochemistry and neuropathology of mice doubly deficient in synthesis and degradation of galactosylceramide. J Neurosci Res 59(2):170-8. [PubMed: 10650875]  [MGI Ref ID J:113298]

Ezoe T; Vanier MT; Oya Y; Popko B; Tohyama J; Matsuda J; Suzuki K; Suzuki K. 2000. Twitcher mice with only a single active galactosylceramide synthase gene exhibit clearly detectable but therapeutically minor phenotypic improvements. J Neurosci Res 59(2):179-87. [PubMed: 10650876]  [MGI Ref ID J:113251]

Galbiati F; Basso V; Cantuti L; Givogri MI; Lopez-Rosas A; Perez N; Vasu C; Cao H; van Breemen R; Mondino A; Bongarzone ER. 2007. Autonomic denervation of lymphoid organs leads to epigenetic immune atrophy in a mouse model of Krabbe disease. J Neurosci 27(50):13730-8. [PubMed: 18077684]  [MGI Ref ID J:130564]

Haq E; Contreras MA; Giri S; Singh I; Singh AK. 2006. Dysfunction of peroxisomes in twitcher mice brain: a possible mechanism of psychosine-induced disease. Biochem Biophys Res Commun 343(1):229-38. [PubMed: 16530726]  [MGI Ref ID J:107482]

Higashi Y; Komiyama A; Suzuki K. 1992. The twitcher mouse: immunocytochemical study of Ia expression in macrophages. J Neuropathol Exp Neurol 51(1):47-57. [PubMed: 1740674]  [MGI Ref ID J:2124]

Huppes W; De Groot CJ; Ostendorf RH; Bauman JG; Gossen JA; Smit V; Vijg J; Dijkstra CD. 1992. Detection of migrated allogeneic oligodendrocytes throughout the central nervous system of the galactocerebrosidase-deficient twitcher mouse. J Neurocytol 21(2):129-36. [PubMed: 1348528]  [MGI Ref ID J:1327]

Igisu H; Suzuki K. 1984. Glycolipids of the spinal cord, sciatic nerve, and systemic organs of the twitcher mouse. J Neuropathol Exp Neurol 43(1):22-36. [PubMed: 6693925]  [MGI Ref ID J:7311]

Igisu H; Suzuki K. 1984. Progressive accumulation of toxic metabolite in a genetic leukodystrophy. Science 224(4650):753-5. [PubMed: 6719111]  [MGI Ref ID J:7427]

Kobayashi T; Yamanaka T; Jacobs JM; Teixeira F; Suzuki K. 1980. The Twitcher mouse: an enzymatically authentic model of human globoid cell leukodystrophy (Krabbe disease). Brain Res 202(2):479-83. [PubMed: 7437911]  [MGI Ref ID J:6423]

Komiyama A; Suzuki K. 1994. Progressive dysfunction of twitcher Schwann cells is evaluated better in vitro than in vivo. Brain Res 637(1-2):106-13. [PubMed: 8180787]  [MGI Ref ID J:17678]

Komiyama A; Suzuki K. 1992. Progressive impairment of Schwann cell proliferation in vitro in murine globoid cell leukodystrophy (twitcher). Brain Res 598(1-2):1-9. [PubMed: 1486471]  [MGI Ref ID J:3584]

LeVine SM; Brown DC. 1997. IL-6 and TNFalpha expression in brains of twitcher, quaking and normal mice. J Neuroimmunol 73(1-2):47-56. [PubMed: 9058758]  [MGI Ref ID J:40116]

LeVine SM; Torres MV. 1992. Morphological features of degenerating oligodendrocytes in twitcher mice. Brain Res 587(2):348-52. [PubMed: 1525668]  [MGI Ref ID J:2125]

LeVine SM; Wetzel DL; Eilert AJ. 1994. Neuropathology of twitcher mice: examination by histochemistry, immunohistochemistry, lectin histochemistry and Fourier transform infrared microspectroscopy. Int J Dev Neurosci 12(4):275-88. [PubMed: 7526605]  [MGI Ref ID J:22147]

Luddi A; Strazza M; Carbone M; Moretti E; Costantino-Ceccarini E. 2005. Galactosylceramidase deficiency causes sperm abnormalities in the mouse model of globoid cell leukodystrophy. Exp Cell Res 304(1):59-68. [PubMed: 15707574]  [MGI Ref ID J:98178]

Luzi P; Rafi MA; Zaka M; Curtis M; Vanier MT; Wenger DA. 2001. Generation of a mouse with low galactocerebrosidase activity by gene targeting: a new model of globoid cell leukodystrophy (Krabbe disease). Mol Genet Metab 73(3):211-23. [PubMed: 11461188]  [MGI Ref ID J:78691]

Matsuda J; Vanier MT; Saito Y; Tohyama J; Suzuki K; Suzuki K. 2001. A mutation in the saposin A domain of the sphingolipid activator protein (prosaposin) gene results in a late-onset, chronic form of globoid cell leukodystrophy in the mouse. Hum Mol Genet 10(11):1191-9. [PubMed: 11371512]  [MGI Ref ID J:78223]

Matsushima GK; Taniike M; Glimcher LH; Grusby MJ; Frelinger JA; Suzuki K; Ting JP. 1994. Absence of MHC class II molecules reduces CNS demyelination, microglial/macrophage infiltration, and twitching in murine globoid cell leukodystrophy. Cell 78(4):645-56. [PubMed: 8069913]  [MGI Ref ID J:19914]

Mohri I; Taniike M; Taniguchi H; Kanekiyo T; Aritake K; Inui T; Fukumoto N; Eguchi N; Kushi A; Sasai H; Kanaoka Y; Ozono K; Narumiya S; Suzuki K; Urade Y. 2006. Prostaglandin D2-mediated microglia/astrocyte interaction enhances astrogliosis and demyelination in twitcher. J Neurosci 26(16):4383-93. [PubMed: 16624958]  [MGI Ref ID J:108359]

Ohno M; Komiyama A; Martin PM; Suzuki K. 1993. MHC class II antigen expression and T-cell infiltration in the demyelinating CNS and PNS of the twitcher mouse. Brain Res 625(2):186-96. [PubMed: 8275302]  [MGI Ref ID J:15111]

Ohno M; Komiyama A; Martin PM; Suzuki K. 1993. Proliferation of microglia/macrophages in the demyelinating CNS and PNS of twitcher mouse. Brain Res 602(2):268-74. [PubMed: 8448672]  [MGI Ref ID J:3948]

Ono J; Harada K; Takahashi M; Maeda M; Ikenaka K; Sakurai K; Sakai N; Kagawa T; Fritz-Zieroth B; Nagai T; Nihei A; Hashimoto S; Okada S. 1995. Differentiation between dysmyelination and demyelination using magnetic resonance diffusional anisotropy. Brain Res 671(1):141-8. [PubMed: 7728526]  [MGI Ref ID J:22996]

Pedchenko TV; LeVine SM. 1999. IL-6 deficiency causes enhanced pathology in Twitcher (globoid cell leukodystrophy) mice. Exp Neurol 158(2):459-68. [PubMed: 10415153]  [MGI Ref ID J:56656]

Pellegatta S; Tunici P; Poliani PL; Dolcetta D; Cajola L; Colombelli C; Ciusani E; Di Donato S; Finocchiaro G. 2006. The therapeutic potential of neural stem/progenitor cells in murine globoid cell leukodystrophy is conditioned by macrophage/microglia activation. Neurobiol Dis 21(2):314-23. [PubMed: 16199167]  [MGI Ref ID J:105739]

Powell HC; Knobler RL; Myers RR. 1983. Peripheral neuropathy in the Twitcher mutant. A new experimental model of endoneurial edema. Lab Invest 49(1):19-25. [PubMed: 6306338]  [MGI Ref ID J:7115]

Sakai N; Inui K; Tatsumi N; Fukushima H; Nishigaki T; Taniike M; Nishimoto J; Tsukamoto H; Yanagihara I; Ozono K; Okada S. 1996. Molecular cloning and expression of cDNA for murine galactocerebrosidase and mutation analysis of the twitcher mouse, a model of Krabbe's disease. J Neurochem 66(3):1118-24. [PubMed: 8769874]  [MGI Ref ID J:31433]

Scaravilli F; Jacobs JM. 1982. Improved myelination in nerve grafts from the leucodystrophic twitcher into trembler mice: evidence for enzyme replacement. Brain Res 237(1):163-72. [PubMed: 7074355]  [MGI Ref ID J:6749]

Scaravilli F; Jacobs JM. 1981. Peripheral nerve grafts in hereditary leukodystrophic mutant mice (twitcher). Nature 290(5801):56-8. [PubMed: 7207584]  [MGI Ref ID J:6477]

Scaravilli F; Suzuki K. 1983. Enzyme replacement in grafted nerve of twitcher mouse. Nature 305(5936):713-5. [PubMed: 6633639]  [MGI Ref ID J:7223]

Shen JS; Watabe K; Ohashi T; Eto Y. 2001. Intraventricular administration of recombinant adenovirus to neonatal twitcher mouse leads to clinicopathological improvements. Gene Ther 8(14):1081-7. [PubMed: 11526455]  [MGI Ref ID J:123201]

Skiba MC; Lyerla TA; Konola JT; Raghavan S. 1990. Somatic cell genetic analysis of the galactocerebrosidase gene: lack of complementation in human Krabbe disease/twitcher mouse cell hybrids. J Neurosci Res 27(4):472-8. [PubMed: 2079710]  [MGI Ref ID J:35073]

Suzuki K; Suzuki K. 1995. The twitcher mouse: a model for Krabbe disease and for experimental therapies. Brain Pathol 5(3):249-58. [PubMed: 8520724]  [MGI Ref ID J:29140]

Suzuki K; Taniike M. 1995. Murine model of genetic demyelinating disease: the twitcher mouse. Microsc Res Tech 32(3):204-14. [PubMed: 8527855]  [MGI Ref ID J:29582]

Takahashi H; Igisu H; Suzuki K; Suzuki K. 1984. Murine globoid cell leukodystrophy: the twitcher mouse. An ultrastructural study of the kidney. Lab Invest 50(1):42-50. [PubMed: 6319815]  [MGI Ref ID J:7313]

Taniike M; Mohri I; Eguchi N; Beuckmann CT; Suzuki K; Urade Y. 2002. Perineuronal oligodendrocytes protect against neuronal apoptosis through the production of lipocalin-type prostaglandin D synthase in a genetic demyelinating model. J Neurosci 22(12):4885-96. [PubMed: 12077186]  [MGI Ref ID J:77531]

Taniike M; Mohri I; Eguchi N; Irikura D; Urade Y; Okada S; Suzuki K. 1999. An apoptotic depletion of oligodendrocytes in the twitcher, a murine model of globoid cell leukodystrophy. J Neuropathol Exp Neurol 58(6):644-53. [PubMed: 10374755]  [MGI Ref ID J:57215]

Taniike M; Suzuki K. 1995. Proliferative capacity of oligodendrocytes in the demyelinating twitcher spinal cord. J Neurosci Res 40(3):325-32. [PubMed: 7745626]  [MGI Ref ID J:23073]

Taniike M; Suzuki K. 1994. Spacio-temporal progression of demyelination in twitcher mouse: with clinico-pathological correlation. Acta Neuropathol (Berl) 88(3):228-36. [PubMed: 7528964]  [MGI Ref ID J:20501]

Taylor RM; Lee JP; Palacino JJ; Bower KA; Li J; Vanier MT; Wenger DA; Sidman RL; Snyder EY. 2006. Intrinsic resistance of neural stem cells to toxic metabolites may make them well suited for cell non-autonomous disorders: evidence from a mouse model of Krabbe leukodystrophy. J Neurochem 97(6):1585-99. [PubMed: 16805770]  [MGI Ref ID J:119020]

Tohyama J; Vanier MT; Suzuki K; Ezoe T; Matsuda J. 2000. Paradoxical influence of acid beta-galactosidase gene dosage on phenotype of the twitcher mouse (genetic galactosylceramidase deficiency) Hum Mol Genet 9(11):1699-707. [PubMed: 10861297]  [MGI Ref ID J:63197]

Whitfield PD; Sharp PC; Taylor R; Meikle P. 2001. Quantification of galactosylsphingosine in the twitcher mouse using electrospray ionization-tandem mass spectrometry. J Lipid Res 42(12):2092-5. [PubMed: 11734583]  [MGI Ref ID J:73367]

Wu YP; McMahon E; Kraine MR; Tisch R; Meyers A; Frelinger J; Matsushima GK; Suzuki K. 2000. Distribution and characterization of GFP(+) donor hematogenous cells in Twitcher mice after bone marrow transplantation. Am J Pathol 156(6):1849-54. [PubMed: 10854208]  [MGI Ref ID J:62662]

Yagi T; Matsuda J; Takikita S; Mohri I; Suzuki K; Suzuki K. 2004. Comparative clinico-pathological study of saposin-A-deficient (SAP-A-/-) and Twitcher mice. J Neuropathol Exp Neurol 63(7):721-34. [PubMed: 15290897]  [MGI Ref ID J:104960]

Yagi T; McMahon EJ; Takikita S; Mohri I; Matsushima GK; Suzuki K. 2004. Fate of donor hematopoietic cells in demyelinating mutant mouse, twitcher, following transplantation of GFP+ bone marrow cells. Neurobiol Dis 16(1):98-109. [PubMed: 15207267]  [MGI Ref ID J:91240]

Yeager AM; Brennan S; Tiffany C; Moser HW; Santos GW. 1984. Prolonged survival and remyelination after hematopoietic cell transplantation in the twitcher mouse. Science 225(4666):1052-4. [PubMed: 6382609]  [MGI Ref ID J:7576]

Yeager AM; Shinn C; Shinohara M; Pardoll DM. 1993. Hematopoietic cell transplantation in the twitcher mouse. The effects of pretransplant conditioning with graded doses of busulfan. Transplantation 56(1):185-90. [PubMed: 8101401]  [MGI Ref ID J:14381]

Zhou D; Cantu C rd; Sagiv Y; Schrantz N; Kulkarni AB; Qi X; Mahuran DJ; Morales CR; Grabowski GA; Benlagha K; Savage P; Bendelac A; Teyton L. 2004. Editing of CD1d-bound lipid antigens by endosomal lipid transfer proteins. Science 303(5657):523-7. [PubMed: 14684827]  [MGI Ref ID J:90443]

Health & husbandry

Health & Colony Maintenance Information

Currently there no information available for this strain. This may be due to the supply level of this strain.

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery of Strains Needing Progeny Testing. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two untested males and two untested females (two pairs) will be recovered, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the overall recovery time to approximately 25 weeks. However, all pups recovered will be sent. Progeny testing is required to identify the genotype of mice of this strain, as a genotyping assay is not available. This type of testing involves breeding the recovered animals and assessing the phenotype of the offspring in order to identify animals carrying the mutation of interest. We can perform the progeny testing for you as a service or we can ship all recovered animals (at least two untested pairs) to you for progeny testing at your facility. If you perform the progeny testing, there is NO guarantee that a carrier will be identified. If we perform progeny testing as a service, additional breeding time will be required. In this case, when a male and female (one pair) are identified that carry the mutation, they and their offspring will be shipped. Delivery time for strains requiring progeny testing often exceeds 25 weeks and may take 12 months or more due to the difficulties in breeding some strains. The progeny testing cost is in addition to the recovery cost and is based on the number of boxes used and the time taken to produce the mice identified as carrying the mutation. Please note that identified pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Please contact Customer Service for more information on the cost of progeny testing for a strain: Tel: 1-800-422-6423 or 1-207-288-5845. Cryorecovery to establish a Dedicated Supply for greater quantities of mice One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. 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
	Untyped from the colony
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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Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
      Surgical Services

Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.