Strain Name:

B6;SJL-Tg(HD)63Aron/J

Stock Number:

004360

Availability:

Repository-Cryopreserved

Use Restrictions Apply, see Terms of Use

Description

Strain Information

Former Names B6;J-Tg(HD)63Aron/J    (Changed: 15-DEC-04 )
B6;SJL-Tg(HD)63Aron    (Changed: 15-DEC-04 )
Type Mutant Strain; Transgenic;
Additional information on Genetically Engineered Mutant Mice.
Specieslaboratory mouse
 
Donating Investigator Neil Aronin,   University of Massachusetts Medical Scho

Description
These transgenic mice express the initial N-terminal third of the mutant human huntingtin gene (IT15) under the direction of the rat neuron-specific enolase promoter. Expected transgene expression was confirmed by Northern blot, RT-PCR and Western blot analysis. Mice heterozygous for the transgene have a phenotype mimicking much of the morphological and subcellular neuropathology that occurs in the striatum and cortex in human Huntington's disease. Behavioral abnormalities are varible in onset and intensity, beginning between three to six months of age. Transgenic mice exhibit increased levels of nuclear and cytoplasmic huntingtin and dysmorphic dendrites in the striatum and cortex. Electron microscopic analysis of nuclear inclusions of cortical and striatal neurons detects granular and filamentous structures that appear to be similar to structures seen in brain affected by Huntington's disease. Cortical stimulation and N-methyl-D-aspartate (NMDA) receptor activation produces abnormal electrophysiological responses from striatal neurons.

Development
A transgenic construct containing bases 316-3210 of the human huntingtin cDNA sequence with a 100 CAG repeat insertion under the control of the rat neuron-specific enolase promoter and an SV40 polyadenylation signal, was introduced into oocyte pronuclei from C57BL/6 X SJL F1 hybrid mice. Transgenic mice were bred to B6;SJL mice.

Control Information

  Control
   Noncarrier
 
  Considerations for Choosing Controls

Related Strains

View Strains carrying other alleles of Eno2     (9 strains)

View Strains carrying other alleles of HTT     (10 strains)

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

View Mammalian Phenotype Terms

Mammalian Phenotype Terms
      assigned by genotype

Tg(HD)63Aron/?

        involves: C57BL/6 * SJL
  • nervous system phenotype
  • abnormal cerebral cortex morphology (MGI Ref ID J:72772)
    • cytoplasmic huntingtin accumulation is prevalent in neurons of the frontal and cingulated cortices and occasionally present in the piriform and hippocampal cortices
    • cortical pyramidal neurons exhibit retraction and disorientation of the apical dendrite, as well as dendritic abnormalities such as beading, small sharp bends, misalignment and bifurcation
  • abnormal excitatory postsynaptic potential (MGI Ref ID J:72772)
    • stimulation of corpus callosum slices evoked smaller EPSPs in striatal neurons as compared to control
    • response to stimulus in striatal neurons results in a rightward shift in the input-output curve (EPSP amplitude) as compared to control
  • abnormal neuron morphology (MGI Ref ID J:72772)
    • one severely affected mouse exhibited shrunken neurons in the hippocampus and cerebellum
    • intracytoplasmic vacuoles and plasma membrane blebs appear in cell bodies and dendrites of neurons with an accumulation of huntingtin
    • abnormal dendrite morphology (MGI Ref ID J:72772)
      • cortical pyramidal neurons exhibit retraction and disorientation of the apical dendrite, as well as dendritic abnormalities such as beading, small sharp bends, misalignment and bifurcation
      • some, but not all, mice exhibit dysmorphic dendrites in hippocampal pyramidal neurons
      • one severely affected mouse had dysmorphic dendrites in cerebellar Purkinje cells
      • dendrites in spiny neurons have significantly more curved endings (J-dendrites) and sharp bends (wavy dendrites) than control
    • abnormal medium spiny neuron morphology (MGI Ref ID J:72772)
      • dendrites in spiny neurons have significantly more curved endings (J-dendrites) and sharp bends (wavy dendrites) than control
    • neuronal intranuclear inclusions (MGI Ref ID J:72772)
      • intranuclear inclusions are detected in the cytoplasm of cortical neurons and to a lesser degree in striatal neurons
      • in a sample of five mice, 27-70% of large striatal neurons that labeled for huntingtin had inclusions
      • nuclear inclusions are composed of granules and filaments as determined by electron microscopy
      • in 11 of 14 mice, inclusions appeared in a few cells in the hippocampus, substantia nigra, cerebellum and brainstem
  • abnormal striatum morphology (MGI Ref ID J:72772)
    • htt staining is substantially increased in the cytoplasm of striatal neurons as compared to control
    • abnormal medium spiny neuron morphology (MGI Ref ID J:72772)
      • dendrites in spiny neurons have significantly more curved endings (J-dendrites) and sharp bends (wavy dendrites) than control
  • enhanced NMDA-mediated synaptic currents (MGI Ref ID J:72772)
    • one population of mutant neurons (most affected) exhibit higher peak currents and current densities when induced by NMDA as well as an increase in calcium ion influx
  • behavior/neurological phenotype
  • abnormal gait (MGI Ref ID J:72772)
    • some mice exhibit an abnormal gait which could include wide-based gait, walking with an arched posture and slow gait
  • abnormal locomotor activation (MGI Ref ID J:72772)
    • some mice exhibit an alteration in activity that is scored as hypo- or hyperactivity
  • impaired coordination (MGI Ref ID J:72772)
    • in rotarod performance
  • limb grasping (MGI Ref ID J:72772)
    • most mice exhibit clasping in the tail suspension test
View Research Applications

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

HTT related

Developmental Biology Research
Neurodevelopmental Defects

Mouse/Human Gene Homologs
Huntington's disease (chorea)

Neurobiology Research
Ataxia (Movement) Defects
Behavioral and Learning Defects
Cortical Defects
Huntington's disease
Neurodegeneration
Neurodevelopmental Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects
Tremor Defects

Genes & Alleles

Gene & Allele Information

Allele Symbol Tg(HD)63Aron
Allele Name transgene insertion 63, Neil Aronin
Allele Type Transgenic (random, expressed)
Common Name(s) HD100L63; TgCAG100;
Mutation Made By Neil Aronin,   University of Massachusetts Medical Scho
Strain of Origin(C57BL/6 x SJL)F1
Expressed Gene HTT, huntingtin, human
Promoter Eno2, enolase 2, gamma, neuronal, rat
General Note Transgenic mice express the initial N-terminal third of the mutant human huntingtin gene (IT15) under the direction of the rat neuron-specific enolase promoter. The phenotype of hemizygous transgenic mice mimicks much of the morphological and subcellularneuropathology that occurs in the striatum and cortex in the human Huntington disease. Onset and intensity of behavioral abnormalities are variable and begin between 3 to 6 months of age.

Transgenic mice exhibit increased levels of nuclear and cytoplasmic huntingtin and dysmorphic dendrites in the striatum and cortex. Electron microscopic analysis of nuclear inclusions of cortical and striatal neurons detects granular and filamentous structures that appear to be similar to structures seen in human brain affected by Huntington's disease. Cortical stimulation and N-methyl-D-aspartate (NMDA) receptor activation produce abnormal electrophysiological responses from striatal neurons of transgenic mice.

Molecular Note The transgene contains bases 316-3210 of the human huntingtin cDNA sequence with a 100 CAG repeat insertion, under the control of the rat neuron-specific enolase promoter and an SV40 polyadenylation signal. Northern blot, RT-PCR, and Western blot analyses detected expression in neural cells. [MGI Ref ID J:72772]

Genotyping

Genotyping Information

Genotyping Protocols

Tg(HD)63Aron, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

Laforet GA; Sapp E; Chase K; McIntyre C; Boyce FM; Campbell M; Cadigan BA; Warzecki L; Tagle DA; Reddy PH; Cepeda C; Calvert CR; Jokel ES; Klapstein GJ; Ariano MA; Levine MS; DiFiglia M; Aronin N. 2001. Changes in cortical and striatal neurons predict behavioral and electrophysiological abnormalities in a transgenic murine model of Huntington's disease. J Neurosci 21(23):9112-23. [PubMed: 11717344]  [MGI Ref ID J:72772]

Additional References

Tg(HD)63Aron related

Ariano MA; Cepeda C; Calvert CR; Flores-Hernandez J; Hernandez-Echeagaray E; Klapstein GJ; Chandler SH; Aronin N; DiFiglia M; Levine MS. 2005. Striatal potassium channel dysfunction in Huntington's disease transgenic mice. J Neurophysiol 93(5):2565-74. [PubMed: 15625098]  [MGI Ref ID J:128569]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & HusbandryThis strain originated on a B6;SJL background and has been backcrossed for 10 generations on the B6;SJL background. Coat color expected from breeding:Black and Agouti
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 $1900.00
*Price(s) in US dollars ($)

Additional Supply Details

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

Additional Supply Details

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.

Control Information

  Control
   Noncarrier
 
  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


See Terms of Use


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Contact Information
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Fax: 207.288.6150
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Terms of Use

Terms of Use


General Terms and Conditions


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Contact information

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fax:207-288-6655

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