Overview

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 five-fold. The Hprt^b-m3 mutation has been used in preimplantation studies to determine when the maternal and paternal alleles of Hprt are activated during early embryonic development. However, the null mutant does not show the characteristics of Lesch-Nyhan disease.

Donating Investigator

Dr. Ted Friedman, UCSD School of Medicine

Genetic overview

Genetic Background	Generation
000664 C57BL/6J

Hprt^b-m3

Allele Type	Gene Symbol	Gene Name
Spontaneous	Hprt	hypoxanthine guanine phosphoribosyl transferase

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Research Applications

Metabolism Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

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 five-fold. The Hprt^b-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.

Development

HPRT ^- embryonic stem cells, derived from the E14TG2a ES cell line, were obtained by selecting for spontaneous mutation by incubation in medium containing 6-thioguanine. Selected ES stem cells were implanted into (C57BL/6Lac X CBA/CaLac) F1 host blastula, and injected blastocysts were fostered in (C57BL/6JLac X CBA/CaLac) F1 females. Germline transmitting chimeras were then crossed with BALB/c mice, and the line was subsequently backcrossed to C57BL/6J for 18 generations.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

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):292-5PubMed: 3821905 MGI: J:15483

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Genetics

Hprt^b-m3

Allele Symbol: Hprt^b-m3

Allele Name	hypoxanthine guanine phosphoribosyl transferase B, mutation 3
Allele Type	Spontaneous
Allele Synonym(s)	Hprt^-
Gene Symbol and Name	Hprt, hypoxanthine guanine phosphoribosyl transferase
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	X
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 Hprt 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 Hprt^b-m3 mutation has been used in preimplantation studies to determine when the maternal and paternal alleles of Hprt 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 Hprt 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.
Mutations Made By	Elizabeth Simpson, Centre for Molecular Medicine & Therapeutics, University of British Columbia

Disease/Phenotype

Disease Terms

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).

Lesch-Nyhan syndrome

Research Areas By Phenotype

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

Genotype: Hprt^b-m3 related

Metabolism Research
Neurobiology Research
- Neurodegeneration

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Hprt^b-m3/Y
involves: 129P2/OlaHsd

behavior/neurological phenotype

abnormal sleep pattern
- mice spend less time sleeping than wild-type mice

increased grooming behavior
- mice exhibit increased grooming time and trauma to the ears and flanks compared to in wild-type mice

The following phenotype relates to a compound genotype created using this strain

Genotype: Hprt^b-m3/Y
B6.129P2-Hprt

nervous system phenotype

abnormal dopaminergic neuron morphology
- dopaminergic neurons from E14 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
- 15% after 2 days in culture to 32% at day 8
- ganglia
- quantitative autoradiographic studies show reductions in the binding of ³H-BTCP to dopamine uptake sites in the caudoputamen of the forebrain but not in the accumbens or olfactory tubercle, suggesting reduced dopamine fiber density in the basal ganglia

homeostasis/metabolism phenotype

decreased dopamine level
- Normal - however, levels of norepinephrine and 5-HT are normal and normal levels of dopamine are seen in the accumbens, olfactory bulbs, and cortex
- 26.2%, 16.5%, and 18.3% reduction in the levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the caudoputamen, diencephalon, and midbrain, respectively, but not in other regions
- mice show a 40% difference in the levels of dopamine in whole-brain extracts after 30 days of age compared to controls
- reduced levels of dopamine in the brain are associated with normal levels of the precursor tyrosine but decreased tyrosine hydroxylation
- 16.4%, 31.9%, 23.1% and 10.8% reduction in the levels of the dopamine metabolite homovanillic acid in the diencephalon, midbrain, cortex, and brainstem, respectively
- 47.5%, 23.7%, 19.9%, and 15.5% reduction in dopamine levels in the caudoputamen, diencephalon, midbrain, and brainstem, respectively

decreased brain choline acetyltransferase activity
- choline acetyltransferase activity is about 16.4% lower in the caudoputamen

decreased brain tyrosine 3-monooxygenase activity
- tyrosine hydroxylase enzyme activity is about 33.1% lower in the caudoputamen and in the cortex

Genotype: Hprt^b-m3/Hprt^b-m3
B6.129P2-Hprt

nervous system phenotype

abnormal dopaminergic neuron morphology
- quantitative autoradiographic studies show reductions in the binding of ³H-BTCP to dopamine uptake sites in the caudoputamen of the forebrain but not in the accumbens or olfactory tubercle, suggesting reduced dopamine fiber density in the basal ganglia
- ganglia

homeostasis/metabolism phenotype

decreased brain tyrosine 3-monooxygenase activity
- tyrosine hydroxylase enzyme activity is about 33.1% lower in the caudoputamen and in the cortex

decreased dopamine level
- 26.2%, 16.5%, and 18.3% reduction in the levels of the dopamine metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the caudoputamen, diencephalon, and midbrain, respectively, but not in other regions
- 16.4%, 31.9%, 23.1% and 10.8% reduction in the levels of the dopamine metabolite homovanillic acid in the diencephalon, midbrain, cortex, and brainstem, respectively
- 47.5%, 23.7%, 19.9%, and 15.5% reduction in dopamine levels in the caudoputamen, diencephalon, midbrain, and brainstem, respectively
- reduced levels of dopamine in the brain are associated with normal levels of the precursor tyrosine but decreased tyrosine hydroxylation
- mice show a 40% difference in the levels of dopamine in whole-brain extracts after 30 days of age compared to controls
- Normal - however, levels of norepinephrine and 5-HT are normal and normal levels of dopamine are seen in the accumbens, olfactory bulbs, and cortex

decreased brain choline acetyltransferase activity
- choline acetyltransferase activity is about 16.4% lower in the caudoputamen

References

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):292-5PubMed: 3821905 MGI: J:15483

Additional References

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):6702-12PubMed: 12944494 MGI: 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):1004-12PubMed: 1777100 MGI: J:1847
Jinnah HA; Page T; Friedmann T. 1993. Brain purines in a genetic mouse model of Lesch-Nyhan disease. J Neurochem 60(6):2036-45PubMed: 8492116 MGI: J:11842
Moore TF; Whittingham DG. 1992. Imprinting of phosphoribosyltransferases during preimplantation development of the mouse mutant, Hprtb-m3. Development 115(4):1011-6PubMed: 1451655 MGI: J:2389
Wu CL; Melton DW. 1993. Production of a model for Lesch-Nyhan syndrome in hypoxanthine phosphoribosyltransferase-deficient mice. Nat Genet 3(3):235-40PubMed: 8485579 MGI: J:4123

Additional - Hprt^b-m3 related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Hprt
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, these mice can be bred as homozygous females and hemizygous males (the gene is X linked). The expected coat color from breeding is black.
- Additional Breeding and Husbandry Support
Appearance
- black
  Related Genotype: a/a
Citation
When using the B6.129P2-Hprt^b-m3/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #002171 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	X linked - Heterozygous Females and Wild-type Males for Hprt1<b-m3>

Related Products and Services

Frozen Mouse Embryo	B6.129P2-Hprt<b-m3>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129P2-Hprt<b-m3>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129P2-Hprt<b-m3>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129P2-Hprt<b-m3>/J Frozen Embryo	$3373.50

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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. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

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Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Hprtb-m3

Allele Symbol: Hprtb-m3

Disease Terms

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).

Research Areas By Phenotype

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

Genotype: Hprtb-m3 related

Mammalian Phenotype Terms by Genotype

Genotype: Hprtb-m3/Yinvolves: 129P2/OlaHsd

behavior/neurological phenotype

Genotype: Hprtb-m3/YB6.129P2-Hprt

nervous system phenotype

homeostasis/metabolism phenotype

Genotype: Hprtb-m3/Hprtb-m3B6.129P2-Hprt

nervous system phenotype

homeostasis/metabolism phenotype

References

Additional References

Additional - Hprtb-m3 related

Genotyping Protocols

Breeding Considerations

Appearance

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

Hprt^b-m3

Allele Symbol: Hprt^b-m3

Genotype: Hprt^b-m3 related

Genotype: Hprt^b-m3/Y
involves: 129P2/OlaHsd

Genotype: Hprt^b-m3/Y
B6.129P2-Hprt

Genotype: Hprt^b-m3/Hprt^b-m3
B6.129P2-Hprt

Additional - Hprt^b-m3 related