Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N11p   Donating Investigator Brian Popko,   University of Chicago

Description
Mice that are homozygous for the targeted mutation have a postnatal lethal phenotype and most do not survive past postnatal day 21 to 28. Surviving homozygotes do not live past 100 days of age. Homozygous female mice are fertile but unable to care for pups. Homozygous male mice are infertile. No gene product (mRNA) is detected by Northern blot analysis of brain tissue from homozygote animals. Mice that are homozygous for the mutation are smaller in size than wildtype and heterozygous littermates. Beginning at 12-14 days of age, homozygotes develop mild ataxia, head jerking movements, and tremors that become more noticeable by 16-20 days of age. The abnormal neurological phenotype is progressive; by 60 days of age many mutants exhibit complete hindlimb paralysis and difficulty breathing. Homozygotes do not synthesize galactolipid galactocerebroside, heterozygotes exhibit reduced levels. Although myelin synthesis and myelin sheath (compact myelin) formation is mostly unaltered in homozygotes, nerve conduction is abnormal in the spinal cord. Electrophysiological analysis of nerve function is consistent with impaired myelin sheath insulative capacity. Histological and electron microscopic analysis reveals vacuolation in the ventral spinal cord and myelin splitting in 24 day old mice. 43 day old mice exhibit more severe myelin splitting, vacuolation of the optic nerve and abnormal node and paranode structure. The electrophysiological and structural abnormalities observed in the CNS are not as severe in the PNS. Levels of peripheral leukocytes and cell numbers in the thymus and spleen are significantly reduced. Spleen, inguinal lymph nodes and Peyer's patches are atrophic. Heterozygotes are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. This mutant mouse strain may be useful in studies of neuroelectrophysiology, nerve myelination and lymphopoiesis in the bone marrow.

Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 2, which encodes the N-terminal region of the enzyme. The construct was electroporated into 129P2/OlaHsd derived BK4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting chimeric male animals were crossed to C57BL/6J mice, and then backcrossed to the same for more than 10 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 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.

Ugt8a^tm1Pop/Ugt8a⁺

        involves: 129P2/OlaHsd * C57BL/6

• homeostasis/metabolism phenotype
• abnormal lipid level (MGI Ref ID J:77226)
  • reduced levels of galactocerebroside and sulfatide at 16 days of age

Ugt8a^tm1Pop/Ugt8a^tm1Pop

        involves: 129P2/OlaHsd * C57BL/6

• life span-post-weaning/aging
• premature death (MGI Ref ID J:77226)
  • some mice died between 18-30 days of age while others survived past 90 d of age
• behavior/neurological phenotype
• abnormal head movements (MGI Ref ID J:77226)
  • mice exhibited jerking movement at 12-14 days of age
• ataxia (MGI Ref ID J:77226)
  • mice displayed mild ataxia at 12-14 days of age
• hindlimb paralysis (MGI Ref ID J:77226)
  • abnormal splaying and dragging of hindlimbs with clenched paws; progressive loss of hindlimb function leading to loss of locomotor ability by 60 d of age
• tremors (MGI Ref ID J:77226)
  • onset between 16-20 days of age; apparent at rest, but more pronounced during movement
• growth/size phenotype
• decreased body weight (MGI Ref ID J:77226)
  • mice weighed 33-66% less than heterozygous and wild-type littermates
• homeostasis/metabolism phenotype
• abnormal lipid level (MGI Ref ID J:77226)
  • absence of galactocerebroside and sulfatide
• immune system phenotype
• *normal* immune system phenotype (MGI Ref ID J:78426)
  • normal natural killer T cell development and function
• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:78426)
  • normal myelin ultrastructure; no vacular degeneration observed in PNS myelin normal myelin ultrastructure; no vacuolar degeneration observed in PNS myelin
• abnormal myelination (MGI Ref ID J:78426)
  • compact myelin displayed at 24 d of age
  • decrease in thickness of dorsal spinal white matter myelin
  • 30% decrease in mean thickness of ventral spinal white matter myelin
  • myelin splitting evident in mice 24 d of age, progression with age
  • vacuolization evident in the ventral region of the spinal cord in mice 24 d of age, progression with age
  • abnormal node and paranode formation
• abnormal nerve conduction (MGI Ref ID J:58935)
  • associated with increased distribution of potassium channel, extending through internodal region
  • 50% reduction in compound action potential amplitude; 30-40% reduction in conductance velocity of sciatic nerve

View Research Applications

Research Applications

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

Developmental Biology Research
Neurodevelopmental Defects

Neurobiology Research
Ataxia (Movement) Defects
Metabolic Defects
Myelination Defects
Neurodevelopmental Defects
Neuromuscular Defects
Tremor Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol		Ugt8atm1Pop
Allele Name		targeted mutation 1, Brian Popko
Allele Type		Targeted (knock-out)
Common Name(s)		Cgt-; Cgt0;
Strain of Origin		129P2/OlaHsd
ES Cell Line Name		BK4
ES Cell Line Strain		129P2/OlaHsd
Gene Symbol and Name		Ugt8a, UDP galactosyltransferase 8A
Chromosome		3
Gene Common Name(s)		AI850488; AW455908; CGT; Cgt; UDP glucuronosyltransferase 8; UDP-galactose ceramide galactosyltransferase; Ugt8; expressed sequence AI850488; expressed sequence AW455908; mCerGT;
Molecular Note		Exon 2 was disrupted by the insertion of a neomycin selection cassette 219 base pairs downstream of the translational start codon. Northern blot analyses showed the exclusive presence of truncated transcript containing the neo transgene in homozgous mutant mice. [MGI Ref ID J:77226]

Genotyping

Genotyping Information

Genotyping Protocols

Ugt8a^tm1Pop, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Coetzee T; Fujita N; Dupree J; Shi R; Blight A; Suzuki K; Suzuki K; Popko B. 1996. Myelination in the absence of galactocerebroside and sulfatide: normal structure with abnormal function and regional instability. Cell 86(2):209-19. [PubMed: 8706126]  [MGI Ref ID J:77226]

Additional References

Ugt8a^tm1Pop related

Coetzee T; Dupree JL; Popko B. 1998. Demyelination and altered expression of myelin-associated glycoprotein isoforms in the central nervous system of galactolipid-deficient mice. J Neurosci Res 54(5):613-22. [PubMed: 9843152]  [MGI Ref ID J:113183]

Coetzee T; Suzuki K; Nave KA; Popko B. 1999. Myelination in the absence of galactolipids and proteolipid proteins. Mol Cell Neurosci 14(1):41-51. [PubMed: 10433816]  [MGI Ref ID J:57688]

Dupree JL; Coetzee T; Blight A; Suzuki K; Popko B. 1998. Myelin galactolipids are essential for proper node of Ranvier formation in the CNS. J Neurosci 18(5):1642-9. [PubMed: 9464989]  [MGI Ref ID J:78426]

Dupree JL; Girault JA; Popko B. 1999. Axo-glial interactions regulate the localization of axonal paranodal proteins. J Cell Biol 147(6):1145-52. [PubMed: 10601330]  [MGI Ref ID J:58935]

Dupree JL; Popko B. 1999. Genetic dissection of myelin galactolipid function. J Neurocytol 28(4-5):271-9. [PubMed: 10739570]  [MGI Ref ID J:61229]

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]

Jahng A; Maricic I; Aguilera C; Cardell S; Halder RC; Kumar V. 2004. Prevention of autoimmunity by targeting a distinct, noninvariant CD1d-reactive T cell population reactive to sulfatide. J Exp Med 199(7):947-57. [PubMed: 15051763]  [MGI Ref ID J:121032]

Katayama Y; Battista M; Kao WM; Hidalgo A; Peired AJ; Thomas SA; Frenette PS. 2006. Signals from the sympathetic nervous system regulate hematopoietic stem cell egress from bone marrow. Cell 124(2):407-21. [PubMed: 16439213]  [MGI Ref ID J:115906]

Katayama Y; Frenette PS. 2003. Galactocerebrosides are required postnatally for stromal-dependent bone marrow lymphopoiesis. Immunity 18(6):789-800. [PubMed: 12818160]  [MGI Ref ID J:84041]

Lullmann-Rauch R; Matzner U; Franken S; Hartmann D; Gieselmann V. 2001. Lysosomal sulfoglycolipid storage in the kidneys of mice deficient for arylsulfatase A (ASA) and of double-knockout mice deficient for ASA and galactosylceramide synthase. Histochem Cell Biol 116(2):161-9. [PubMed: 11685544]  [MGI Ref ID J:120809]

Marcus J; Dupree JL; Popko B. 2000. Effects of galactolipid elimination on oligodendrocyte development and myelination. Glia 30(4):319-28. [PubMed: 10797612]  [MGI Ref ID J:113081]

Marcus J; Dupree JL; Popko B. 2002. Myelin-associated glycoprotein and myelin galactolipids stabilize developing axo-glial interactions. J Cell Biol 156(3):567-77. [PubMed: 11827985]  [MGI Ref ID J:77227]

Poliak S; Gollan L; Salomon D; Berglund EO; Ohara R; Ranscht B; Peles E. 2001. Localization of Caspr2 in myelinated nerves depends on axon-glia interactions and the generation of barriers along the axon. J Neurosci 21(19):7568-75. [PubMed: 11567047]  [MGI Ref ID J:124251]

Schafer DP; Bansal R; Hedstrom KL; Pfeiffer SE; Rasband MN. 2004. Does paranode formation and maintenance require partitioning of neurofascin 155 into lipid rafts? J Neurosci 24(13):3176-85. [PubMed: 15056697]  [MGI Ref ID J:109788]

Stanic AK; De Silva AD; Park JJ; Sriram V; Ichikawa S; Hirabyashi Y; Hayakawa K; Van Kaer L; Brutkiewicz RR; Joyce S. 2003. Defective presentation of the CD1d1-restricted natural Va14Ja18 NKT lymphocyte antigen caused by beta-D-glucosylceramide synthase deficiency. Proc Natl Acad Sci U S A 100(4):1849-54. [PubMed: 12576547]  [MGI Ref ID J:81972]

Tadano-Aritomi K; Hikita T; Fujimoto H; Suzuki K; Motegi K; Ishizuka I. 2000. Kidney lipids in galactosylceramide synthase-deficient mice. Absence Of galactosylsulfatide and compensatory increase in more polar sulfoglycolipids J Lipid Res 41(8):1237-43. [PubMed: 10946011]  [MGI Ref ID J:64029]

Traka M; Dupree JL; Popko B; Karagogeos D. 2002. The neuronal adhesion protein TAG-1 is expressed by Schwann cells and oligodendrocytes and is localized to the juxtaparanodal region of myelinated fibers. J Neurosci 22(8):3016-24. [PubMed: 11943804]  [MGI Ref ID J:125653]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	When maintaining a live colony, these mice are bred as heterozygotes due to the homozygous postnatal lethal phenotype. Homozygous female mice are fertile but unable to care for pups. Homozygous male mice are infertile.

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 - Standard. 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 males and two females (two pairs) will be provided, 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 delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that 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. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. 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 Induced Mutant Resource Colony collection.

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

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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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Fax: 207.288.6150
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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.”

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