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Former Names B6;129-Hprttm1Detl/J (Changed: 15-DEC-04 ) Type Mutant Stock; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse Generation N?+1F5+F1n1P (08-JAN-04) Donating Investigator Peter Detloff, University of Alabama at Birmingham Description
Mutant mice develop a phenotype similar to the human translated CAG repeat disorders showing a late onset neurological phenotype. Mice have handling-induced seizures, weight gain, reduced vertical activity, clasping response, impaired performance on the rotarod task, and premature death. Mice subjected to frequent handling have a median age of death of 45 weeks. There is the presence of neuronal intranuclear inclusions containing at least part of the polyglutamine-containing HPRT protein and ubiquitin. These results indicate that expanded CAG repeats need not be located within one of the classic repeat disorder genes to have a neurotoxic effect. Note that the size of the CAG repeat may not be stable and any reduction in repeat size may lead to a later onset phenotype.
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 101045 B6129SF2/J | (approximate) | |
| Wildtype mice from the colony or B6129SF2/J colony (Stock No. 101045) may be used as controls. The B6129SF2 mice only provide an approximate genetic match to this B6,129 background. | ||
| Considerations for Choosing Controls | ||
Strains carrying other alleles of Hprt1
004302 129S1-Hprt1tm1(cre)Mnn/J 002027 129S8/SvEv-Gpi1c Hprt1b-m2/J 002171 B6.129P2-Hprt1b-m3/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 000807 RBJ/DnJ View Strains carrying other alleles of Hprt1 (11 strains)
View Mammalian Phenotype Terms
Mammalian Phenotype Terms
assigned by genotype
Hprt1tm1Detl/Hprt1tm1Detl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
- life span-post-weaning/aging
- premature death (MGI Ref ID J:44728)
- median age of death of mutants is 45 weeks, with all animals dying by 53 weeks
- behavior/neurological phenotype
- abnormal motor capabilities/coordination/movement (MGI Ref ID J:44728)
- when suspended by tail, mice tend to escape by climbing up experimenter's fingers, but by 18 weeks of age, mutants have lost this ability
- abnormal gait (MGI Ref ID J:44728)
- some mice have a swaying gait, after onset of ataxia
- abnormal involuntary movement (MGI Ref ID J:44728)
- mice observed at 44-48 weeks showed frequent jerks of the body
- limb grasping (MGI Ref ID J:44728)
- many mutants display limb clasping upon tail suspension; clasping is involuntary and tends to be more frequent in older mice
- when lowered into cage, limbs remain clasped rather than being outstretched as observed in controls; impairment increases with age of mutant
- tremors (MGI Ref ID J:44728)
- mice at 44-48 weeks display a slight resting tremor, preceding ataxia
- ataxia (MGI Ref ID J:44728)
- me mice aged between 44 and 48 weeks exhibit slight ataxia characterized by a swaying gait
- onset of ataxia is typically followed by death within 3-6 days
- decreased vertical activity (MGI Ref ID J:44728)
- mutant mice exhibit progressively less vertical activity as they age
- impaired coordination (MGI Ref ID J:44728)
- older mutants (>18 weeks) tend to fall off rod in rotarod paradigm to larger extent than younger mutants or age-matched controls; impairment increases with age of mutant
- decreased exploration in new environment (MGI Ref ID J:44728)
- after 18 weeks of age, mutants have lower exploratory activity in cages when lid and food rack are removed
- seizures (MGI Ref ID J:44728)
- some older mice (>18 weeks of age) display seizures but mice younger than 18 weeks do not exhibit seizure activity
- 7 mice were assayed to determine penetrance of seizure susceptibility; 4/7 experienced at least one seizure by 21 weeks of age, and all 7 had at least one seizure by 35 weeks
- convulsive seizures (MGI Ref ID J:44728)
- handling of mice sometimes causes a convulsive episode; seizures on average started ~36 seconds after suspension by the tail and last ~42 seconds
- nervous system phenotype
- abnormal brain morphology (MGI Ref ID J:44728)
- in brains of affected mice aged 30-46 weeks, a densely staining (with Hprt antibody) mass in nuclei in many neurons, but this is never observed in control animals
- brain size/weight is normal compared to controls
- neuronal intranuclear inclusions (MGI Ref ID J:44728)
- neuronal intranuclear inclusions (NIIs) are seen in many neurons in many brain regions; most neurons only contain 1 NII
- ~30% of neurons in pyramidal layer of cerebral cortex contain an NII, while only 6% of neurons in deeper layers contain them
- seizures (MGI Ref ID J:44728)
- some older mice (>18 weeks of age) display seizures but mice younger than 18 weeks do not exhibit seizure activity
- 7 mice were assayed to determine penetrance of seizure susceptibility; 4/7 experienced at least one seizure by 21 weeks of age, and all 7 had at least one seizure by 35 weeks
- convulsive seizures (MGI Ref ID J:44728)
- handling of mice sometimes causes a convulsive episode; seizures on average started ~36 seconds after suspension by the tail and last ~42 seconds
- liver/biliary system phenotype
- hepatic steatosis (MGI Ref ID J:44728)
- mice (2/2 females examined between 34 and 38 weeks) exhibit moderately fatty livers
Hprt1tm1Detl/Y
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J
- life span-post-weaning/aging
- premature death (MGI Ref ID J:44728)
- median age of death of mutants is 45 weeks, with all animals dying by 53 weeks
- growth/size phenotype
- increased body weight (MGI Ref ID J:44728)
- at 23 weeks, males weigh more than age-matched WT male controls
- behavior/neurological phenotype
- abnormal motor capabilities/coordination/movement (MGI Ref ID J:44728)
- when suspended by tail, mice tend to escape by climbing up experimenter's fingers, but by 18 weeks of age, mutants have lost this ability
- abnormal gait (MGI Ref ID J:44728)
- some mice have a swaying gait, with development of ataxia
- abnormal involuntary movement (MGI Ref ID J:44728)
- mice observed at 44-48 weeks showed frequent jerks of the body
- limb grasping (MGI Ref ID J:44728)
- many mutants display limb clasping upon tail suspension; clasping is involuntary and tends to be more frequent in older mice
- when lowered into cage, limbs remain clasped rather than being outstretched as observed in controls; impairment increases with age of mutant
- tremors (MGI Ref ID J:44728)
- some mice at 44-48 weeks display a slight resting tremor, preceding ataxia
- ataxia (MGI Ref ID J:44728)
- some mice aged between 44 and 48 weeks exhibit slight ataxia characterized by a swaying gait
- onset of ataxia is typically followed by death within 3-6 days
- decreased vertical activity (MGI Ref ID J:44728)
- mutant mice exhibit progressively less vertical activity as they age
- impaired coordination (MGI Ref ID J:44728)
- older mutants (>18 weeks) tend to fall off rod in rotarod paradigm to greater extent than younger mutants or age-matched controls; impairment increases with age of mutant
- decreased exploration in new environment (MGI Ref ID J:44728)
- after 18 weeks of age, mutants have lower exploratory activity in cages when lid and food rack are removed
- seizures (MGI Ref ID J:44728)
- some older mice (>18 weeks of age) display seizures but mice younger than 18 weeks do not exhibit seizure activity
- 7 mice were assayed to determine penetrance of seizure susceptibility; 4/7 experienced at least one seizure by 21 weeks of age, and all 7 had at least one seizure by 35 weeks
- convulsive seizures (MGI Ref ID J:44728)
- handling of mice sometimes causes a convulsive episode; seizures on average started ~36 seconds after suspension by the tail and last ~42 seconds
- nervous system phenotype
- abnormal brain morphology (MGI Ref ID J:44728)
- in brains of affected mice aged 30-46 weeks, a densely staining (with Hprt antibody) mass in nuclei in many neurons, but this is never observed in control animals
- brain size/weight is normal compared to controls
- neuronal intranuclear inclusions (MGI Ref ID J:44728)
- neuronal intranuclear inclusions (NIIs) are seen in many neurons in many brain regions; most neurons only contain 1 NII
- ~30% of neurons in pyramidal layer of cerebral cortex contain an NII, while only 6% of neurons in deeper layers contain them
- seizures (MGI Ref ID J:44728)
- some older mice (>18 weeks of age) display seizures but mice younger than 18 weeks do not exhibit seizure activity
- 7 mice were assayed to determine penetrance of seizure susceptibility; 4/7 experienced at least one seizure by 21 weeks of age, and all 7 had at least one seizure by 35 weeks
- convulsive seizures (MGI Ref ID J:44728)
- handling of mice sometimes causes a convulsive episode; seizures on average started ~36 seconds after suspension by the tail and last ~42 seconds
- reproductive system phenotype
- testicular atrophy (MGI Ref ID J:44728)
- 1/2 males at 34-38 weeks displayed complete testicular atrophy but other male was normal
- endocrine/exocrine gland phenotype
- testicular atrophy (MGI Ref ID J:44728)
- 1/2 males at 34-38 weeks displayed complete testicular atrophy but other male was normal
- liver/biliary system phenotype
- hepatic steatosis (MGI Ref ID J:44728)
- mice (2/2 males examined between 34 and 38 weeks) exhibit moderately fatty livers
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:
Hprt1tm1Detl relatedMouse/Human Gene Homologs
Lesch-Nyhan syndrome
Metabolism Research
Neurobiology Research
Neurodegeneration
| Allele Symbol | Hprt1tm1Detl | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Peter J Detloff | ||
| Allele Type | Targeted (knock-in) | ||
| Common Name(s) | JO1; hprt(CAG)146; | ||
| Mutation Made By | Peter Detloff, University of Alabama at Birmingham | ||
| Strain of Origin | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| ES Cell Line Name | R1 | ||
| ES Cell Line Strain | (129X1/SvJ x 129S1/Sv)F1-Kitl<+> | ||
| 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; | ||
| Molecular Note | A construct was created that introduced a long CAG repeat (n=146 units) into an Xho1 site in exon 3 of a genomic fragment of the locus. An additional 4.9kb genomic fragment, which included exon 4 of the gene, was added to this repeat-containing construct. Appropriately targeted clones had sequences containing the 146-unit CAG repeat, encoding a stretch of 146 glutamines, in place of wild-type exon 3. [MGI Ref ID J:44728] | ||
Genotyping Protocols
Hprt1tm1Detl, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
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]
Hprt1tm1Detl relatedJenkins BG; Andreassen OA; Dedeoglu A; Leavitt B; Hayden M; Borchelt D; Ross CA; Ferrante RJ; Beal MF. 2005. Effects of CAG repeat length, HTT protein length and protein context on cerebral metabolism measured using magnetic resonance spectroscopy in transgenic mouse models of Huntington's disease. J Neurochem 95(2):553-62. [PubMed: 16135087] [MGI Ref ID J:129784]
Tallaksen-Greene SJ; Crouse AB; Hunter JM; Detloff PJ; Albin RL. 2005. Neuronal intranuclear inclusions and neuropil aggregates in Hdh(CAG(150)) knockin mice. Neuroscience 131(4):843-52. [PubMed: 15749339] [MGI Ref ID J:96770]
Tallaksen-Greene SJ; Ordway JM; Crouse AB; Jackson WS; Detloff PJ; Albin RL. 2003. Hprt(CAG)146 mice: age of onset of behavioral abnormalities, time course of neuronal intranuclear inclusion accumulation, neurotransmitter marker alterations, mitochondrial function markers, and susceptibility to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. J Comp Neurol 465(2):205-19. [PubMed: 12949782] [MGI Ref ID J:85583]
Colony Maintenance
Diet Information LabDiet® 5K52/5K67
| Pricing for USA, Canada and Mexico shipping destinations |
|
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. |
|---|---|
| Supply Notes |
|
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| 101045 B6129SF2/J | (approximate) | |
| Wildtype mice from the colony or B6129SF2/J colony (Stock No. 101045) may be used as controls. The B6129SF2 mice only provide an approximate genetic match to this B6,129 background. | ||
| 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. | ||
Purchasing Information
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