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Former Names B6.129P2-Hprtb-m3/J (Changed: 15-DEC-04 ) Type Chemically Induced Mutation; Congenic; Mutant Strain; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Background Strain C57BL/6J Donor Strain 129P2 via E14TG2a ES cell line Donating Investigator Ted Friedman, UCSD School of Medicine Appearance
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Related Genotype: a/aDescription
HPRT-embryonic stem cells were obtained by selecting for spontaneous mutation by incubation in medium containing 6-thioguanine. HPRT-males have no overt phenotype of abnormal behavior. The mutation is due to a large deletion in the Hprt gene. Mutant mice have no HPRT detectable by Western blot analysis and no detectable HPRT enzyme activity in brain homogenates. They appear to have normal brain purine content, but de novo purine synthesis is accelerated four- to fivefold. The Hprtb-m3 mutation has been used in preimplantation studies to determine when the maternal and paternal alleles of Hprt are activated during early embryonic development. Either administration of amphetamine or inhibition of adenine phosphoribosyltransferase (APRT) activity stimulates locomotor and stereotypic behaviors in HPRT-deficient mice. However, the null mutant for both Hprt and Aprt does not show the characteristics of Lesch-Nyhan disease.
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Hprt1
004302 129S1-Hprt1tm1(cre)Mnn/J 002027 129S8/SvEv-Gpi1c Hprt1b-m2/J 008710 B6.129P2-Hprt1tm10(Ple162-EGFP/cre)Ems/J 008877 B6.129P2-Hprt1tm12(Ple177-EGFP/cre)Ems/J 008706 B6.129P2-Hprt1tm4(Ple88-EGFP)Ems/J 008707 B6.129P2-Hprt1tm7(Ple185-EGFP)Ems/J 008708 B6.129P2-Hprt1tm8(Ple151-EGFP)Ems/J 008709 B6.129P2-Hprt1tm9(Ple178-EGFP/cre)Ems/J 008876 B6;129-Hprt1tm11(Ple176-EGFP/cre)Ems/J 003138 B6;129-Hprt1tm1Detl/J 000807 RBJ/DnJ View Strains carrying other alleles of Hprt1 (11 strains)
View Related Disease (OMIM) Terms
Related Disease (OMIM) Terms
Lesch-Nyhan Syndrome; LNS - 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
Hprt1b-m3/Y
B6.129P2-Hprt1b-m3
- nervous system phenotype
- abnormal dopaminergic neuron morphology (MGI Ref ID J:107966)
- dopaminergic neurons from E14 Hprt-deficient mice differentiate in culture, but dendrite outgrowth is decelerated and the average dendrite length per neuron is lower than in control neurons; the difference in length increased over time in culture with the deficit being 15% after 2 days in culture to 32% at day 8
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Hprt1b-m3/Y
involves: 129P2/OlaHsdView Research Applications
Research Applications
This mouse can be used to support research in many areas including:Hprt1b-m3 related
Metabolism Research
Neurobiology Research
Neurodegeneration
| Allele Symbol | Hprt1b-m3 | ||
|---|---|---|---|
| Allele Name | hypoxanthine guanine phosphoribosyl transferase B, mutation 3 | ||
| Allele Type | Spontaneous | ||
| Mutation Made By | Ted Friedman, UCSD School of Medicine | ||
| Strain of Origin | 129P2/OlaHsd | ||
| ES Cell Line Name | E14TG2a | ||
| ES Cell Line Strain | 129P2/OlaHsd | ||
| Gene Symbol and Name | Hprt1, hypoxanthine guanine phosphoribosyl transferase 1 | ||
| Chromosome | X | ||
| Gene Common Name(s) | C81579; HGPRT; HPGRT; HPRT; Hgprtase; MGC112554; expressed sequence C81579; | ||
| General Note | HPRT- embryonic stem cells were obtained by selecting for spontaneous mutation by incubation in medium containing 6-thioguanine. HPRT- males have no overt phenotype of abnormal behavior (J:15483). The mutation is due to a large deletion in the Hprt1 gene. In situ hybridization studies showed HPRT mRNA in high levels in most neurons, but not in glial cells, in normal mice. No HPRT mRNA was detected in the brains of male mice carrying this deletion (J:2058). Mutant mice have no HPRT detectable by Western blot analysis and no detectable HPRT enzyme activity in brain homogenates. They appear to have normal brain purine content, but de novo purine synthesis is accelerated four- to fivefold (J:11842). The Hprt1b-m3 mutation has been used in preimplantation studies to determine when the maternal and paternal alleles of Hprt1 are activated during early embryonic development (J:2389). Either administration of amphetamine (J:1847) or inhibition of adenine phosphoribosyltransferase (APRT) activity (J:4123) stimulates locomotor and stereotypic behaviors in HPRT-deficient mice. However, the null mutant for both Hprt1 and Aprt does not show the characteristics of Lesch-Nyhan disease (J:35822).Cells from mice hemizygous or homozygous for this mutation are HPRT-deficient and resistant to the drug 6-thioguanine (6TG). | ||
| Molecular Note | The allele contains a ~55 kb deletion spanning the promoter and first 2 exons. Subsequent direct sequence comparison with wild type DNA defined the exact breakpoints of the deletion, which lies 415 bp after the 3' end of Exon 2, and determined the deletion size to be 36 kb. [MGI Ref ID J:144244] [MGI Ref ID J:41459] | ||
This strain will not have a genotyping protocol or one is not currently available.
Helpful Links
Genotyping resources and troubleshooting
Hooper M; Hardy K; Handyside A; Hunter S; Monk M. 1987. HPRT-deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature 326(6110):292-5. [PubMed: 3821905] [MGI Ref ID J:15483]
Gu JJ; Tolin AK; Jain J; Huang H; Santiago L; Mitchell BS. 2003. Targeted disruption of the inosine 5'-monophosphate dehydrogenase type I gene in mice. Mol Cell Biol 23(18):6702-12. [PubMed: 12944494] [MGI Ref ID J:85443]
Jinnah HA; Gage FH; Friedmann T. 1991. Amphetamine-induced behavioral phenotype in a hypoxanthine-guanine phosphoribosyltransferase-deficient mouse model of Lesch-Nyhan syndrome. Behav Neurosci 105(6):1004-12. [PubMed: 1777100] [MGI Ref ID J:1847]
Jinnah HA; Page T; Friedmann T. 1993. Brain purines in a genetic mouse model of Lesch-Nyhan disease. J Neurochem 60(6):2036-45. [PubMed: 8492116] [MGI Ref ID J:11842]
Moore TF; Whittingham DG. 1992. Imprinting of phosphoribosyltransferases during preimplantation development of the mouse mutant, Hprtb-m3. Development 115(4):1011-6. [PubMed: 1451655] [MGI Ref ID J:2389]
Wu CL; Melton DW. 1993. Production of a model for Lesch-Nyhan syndrome in hypoxanthine phosphoribosyltransferase-deficient mice. Nat Genet 3(3):235-40. [PubMed: 8485579] [MGI Ref ID J:4123]
Hprt1b-m3 relatedBoer P; Brosh S; Wasserman L; Hammel I; Zoref-Shani E; Sperling O. 2001. Decelerated rate of dendrite outgrowth from dopaminergic neurons in primary cultures from brains of hypoxanthine phosphoribosyltransferase-deficient knockout mice. Neurosci Lett 303(1):45-8. [PubMed: 11297820] [MGI Ref ID J:107966]
Egami K; Yitta S; Kasim S; Lewers JC; Roberts RC; Lehar M; Jinnah HA. 2007. Basal ganglia dopamine loss due to defect in purine recycling. Neurobiol Dis 26(2):396-407. [PubMed: 17374562] [MGI Ref ID J:134847]
Engle SJ; Womer DE; Davies PM; Boivin G; Sahota A; Simmonds HA; Stambrook PJ; Tischfield JA. 1996. HPRT-APRT-deficient mice are not a model for lesch-nyhan syndrome. Hum Mol Genet 5(10):1607-10. [PubMed: 8894695] [MGI Ref ID J:35822]
Gu JJ; Stegmann S; Gathy K; Murray R; Laliberte J; Ayscue L; Mitchell BS. 2000. Inhibition of T lymphocyte activation in mice heterozygous for loss of the IMPDH II gene. J Clin Invest 106(4):599-606. [PubMed: 10953035] [MGI Ref ID J:86045]
Gu JJ; Tolin AK; Jain J; Huang H; Santiago L; Mitchell BS. 2003. Targeted disruption of the inosine 5'-monophosphate dehydrogenase type I gene in mice. Mol Cell Biol 23(18):6702-12. [PubMed: 12944494] [MGI Ref ID J:85443]
Jinnah HA; Gage FH; Friedmann T. 1991. Amphetamine-induced behavioral phenotype in a hypoxanthine-guanine phosphoribosyltransferase-deficient mouse model of Lesch-Nyhan syndrome. Behav Neurosci 105(6):1004-12. [PubMed: 1777100] [MGI Ref ID J:1847]
Jinnah HA; Hess EJ; Wilson MC; Gage FH; Friedmann T. 1992. Localization of hypoxanthine-guanine phosphoribosyltransferase messenger RNA in the mouse brain by insitu hybridization Mol Cell Neurosci 3(1):64-78. [MGI Ref ID J:2058]
Jinnah HA; Jones MD; Wojcik BE; Rothstein JD; Hess EJ; Friedmann T; Breese GR. 1999. Influence of age and strain on striatal dopamine loss in a genetic mouse model of Lesch-Nyhan disease. J Neurochem 72(1):225-9. [PubMed: 9886073] [MGI Ref ID J:51651]
Jinnah HA; Page T; Friedmann T. 1993. Brain purines in a genetic mouse model of Lesch-Nyhan disease. J Neurochem 60(6):2036-45. [PubMed: 8492116] [MGI Ref ID J:11842]
Kuehn MR; Bradley A; Robertson EJ; Evans MJ. 1987. A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice. Nature 326(6110):295-8. [PubMed: 3029599] [MGI Ref ID J:15485]
Mikolaenko I; Rao LM; Roberts RC; Kolb B; Jinnah HA. 2005. A Golgi study of neuronal architecture in a genetic mouse model for Lesch-Nyhan disease. Neurobiol Dis 20(2):479-90. [PubMed: 15908225] [MGI Ref ID J:102545]
Moore TF; Whittingham DG. 1992. Imprinting of phosphoribosyltransferases during preimplantation development of the mouse mutant, Hprtb-m3. Development 115(4):1011-6. [PubMed: 1451655] [MGI Ref ID J:2389]
Ordway JM; Tallaksen-Greene S; Gutekunst CA; Bernstein EM; Cearley JA; Wiener HW; Dure LS 4th; Lindsey R; Hersch SM; Jope RS; Albin RL; Detloff PJ. 1997. Ectopically expressed CAG repeats cause intranuclear inclusions and a progressive late onset neurological phenotype in the mouse. Cell 91(6):753-63. [PubMed: 9413985] [MGI Ref ID J:44728]
Tsuda H; Maynard-Currie CE; Reid LH; Yoshida T; Edamura K; Maeda N ; Smithies O ; Jakobovits A. 1997. Inactivation of the mouse HPRT locus by a 203-bp retroposon insertion and a 55-kb gene-targeted deletion: establishment of new HPRT-deficient mouse embryonic stem cell lines. Genomics 42(3):413-21. [PubMed: 9205113] [MGI Ref ID J:41459]
Tucker KL; Wang Y; Dausman J; Jaenisch R. 1997. A transgenic mouse strain expressing four drug-selectable marker genes. Nucleic Acids Res 25(18):3745-6. [PubMed: 9278500] [MGI Ref ID J:92995]
Visser JE; Smith DW; Moy SS; Breese GR; Friedmann T; Rothstein JD; Jinnah HA. 2002. Oxidative stress and dopamine deficiency in a genetic mouse model of Lesch--Nyhan disease. Brain Res Dev Brain Res 133(2):127-39. [PubMed: 11882343] [MGI Ref ID J:75479]
Williamson DJ; Hooper ML; Melton DW. 1992. Mouse models of hypoxanthine phosphoribosyltransferase deficiency. J Inherit Metab Dis 15(4):665-73. [PubMed: 1528024] [MGI Ref ID J:3354]
Wu CL; Melton DW. 1993. Production of a model for Lesch-Nyhan syndrome in hypoxanthine phosphoribosyltransferase-deficient mice. Nat Genet 3(3):235-40. [PubMed: 8485579] [MGI Ref ID J:4123]
Yang GS; Banks KG; Bonaguro RJ; Wilson G; Dreolini L; de Leeuw CN; Liu L; Swanson DJ; Goldowitz D; Holt RA; Simpson EM. 2008. Next generation tools for high-throughput promoter and expression analysis employing single-copy knock-ins at the Hprt1 locus. Genomics :. [PubMed: 18950699] [MGI Ref ID J:144244]
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
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Animals Provided
Price (US dollars $) Cryorecovery Fee $1900.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
| Pricing for International shipping destinations |
|
Animals Provided
Price (US dollars $) Cryorecovery Fee $2470.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
| Standard Supply | Cryopreserved. Ready for recovery. Please refer to pricing and supply notes for further information. |
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| Supply Notes |
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| Control | ||
|---|---|---|
| 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. | ||
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