Strain Name:

B6;129-Hprt1tm1Detl/J

Stock Number:

003138

Availability:

Repository-Cryopreserved

Description

Strain Information

Former Names B6;129-Hprttm1Detl/J    (Changed: 15-DEC-04 )
Type Mutant Stock; Targeted Mutation;
Specieslaboratory mouse
GenerationN?+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 Information

  Allele   Control
 Hprt1tm1Detl  Wild-type from the colony
 Hprt1tm1Detl  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

Related Strains

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
000807   RBJ/DnJ
View Strains carrying other alleles of Hprt1     (4 strains)

Phenotype

Phenotype Information

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

Research Applications

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

Mouse/Human Gene Homologs
Lesch-Nyhan syndrome

Hprt1tm1Detl related

Metabolism Research

Neurobiology Research
Neurodegeneration

Genes & Alleles

Gene & Allele Information

Allele Symbol Hprt1tm1Detl
Allele Name targeted mutation 1, Peter J Detloff
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 NameR1
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; 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

Genotyping Information

Genotyping Protocols

Hprttm1Detl, , vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

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]

Additional References

Hprt1tm1Detl related

Jenkins 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]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Pricing for USA, Canada and Mexico shipping destinations             View   International   Pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $1900.00
*Price(s) in US dollars ($)

Supply Details

Standard SupplyRepository-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.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

Pricing for International shipping destinations             View   USA, Canada and Mexico   Pricing
Weeks of AgePrice*Gender
Cryorecovery Fee $2470.00
*Price(s) in US dollars ($)

Supply Details

Standard SupplyRepository-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.
  • Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

  Allele   Control
 Hprt1tm1Detl  Wild-type from the colony
 Hprt1tm1Detl  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.

General Terms and Conditions

View JAX® Mice & Services Conditions 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.
Ordering and Purchasing Information

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Contact Information
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Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
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