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Strain Name:

B6.129S4-Cdk5r1tm1Lht/J

Stock Number:

004163

Availability:

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Former Name      B6.129S4-Cdk5rtm1Lht/J    (Changed: 17-FEB-05 )
Genes & Alleles   Cdk5r1;   Cdk5r1tm1Lht;

Product Information

Strain Details

Type JAX® GEMM® Strain - Congenic
Additional information on JAX® GEMM® Strains.
Type JAX® GEMM® Strain - Mutant Strain
Type JAX® GEMM® Strain - Targeted Mutation
Specieslaboratory mouse
Donating Investigator Li-Huei Tsai,   Harvard Medical School
GenerationN5F?+4pN1 (15-FEB-04)

Strain Description
At birth, mice homozygous for this targeted allele are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Cdk5r protein product is not immunodetectable in homozygote whole-brain lysates. Histological analysis of homozygotes reveals severe defects in the patterning of the cerebral cortex and other areas of the brain. The normal lamination pattern of cortical neurons is disrupted; axonal trajectories and dendritic structures are altered. Homozygous mice are more susceptible to mortality from chemically induced-seizures. Sporadic adult lethality is also observed, presumably resulting from spontaneous seizures, a consequence of the disrupted cytoarchitecture observed in the cortex. This mutant mouse strain represents a model that may be useful in studies related to the mechanisms of cortical lamination, epilepsy, Alzheimer's and other neurodegenerative diseases.

Strain Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt the entire Cdk5r open reading frame and 400 bp of downstream sequence. The construct was electroporated into 129S4/SvJae-derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts. The resulting chimeric male animals were backcrossed to female C57BL/6 mice.

Mammalian Phenotype Terms assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.

Cdk5r1tm1Lht/Cdk5r1tm1Lht

        involves: 129S4/SvJae * C57BL/6
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:38857)
    • ~15% of homozygotes die by ~4 months, starting at about 3 weeks of age
  • nervous system phenotype
  • abnormal cerebellar molecular layer (MGI Ref ID J:38857)
    • molecular layer shows a greater cell density than wild-type, and contains cells resembling granule cells
  • abnormal forebrain morphology (MGI Ref ID J:38857)
    • in three-month old mice, general disorganization of forebrain is apparent
    • abnormal cerebral cortex morphology (MGI Ref ID J:38857)
      • laminated structure is not apparent in 3-month old mice; defects in lamination are less severe in lateral-ventral region of cortex
      • no recognizable pattern is observed for distribution of pyramidal, granule, and polymorphic cells in cortex
      • mutant cortex contains aberrant fascicles in the neocortex and no fascicles are seen in the lateral-ventral portion of the cortex
      • radial distribution of pyramidal neurons and their apical dendrites is not conspicuous like in wild-type brains
      • cortex shows mild neuronal-positioning abnormalities
      • abnormal pyramidal neuron morphology (MGI Ref ID J:38857)
        • orientation of neuronal soma and direction of dendritic growth are altered; defect is more severe in medial neocortex
    • abnormal hippocampus morphology (MGI Ref ID J:38857)
      • at E18.5, hippocampus shows signs of disorganization, but this is less severe than in double null mutants
      • abnormal dentate gyrus morphology (MGI Ref ID J:38857)
      • abnormal hippocampal laminar structure (MGI Ref ID J:38857)
        • layers II and III are occupied by large instead of small pyramidal neurons
        • most cells in hippocampus and dentate gyrus are included in a laminar structure like in wild-type, but cells are less densely packed
      • abnormal pyramidal neuron morphology (MGI Ref ID J:38857)
        • orientation of neuronal soma and direction of dendritic growth are altered; defect is more severe in medial neocortex
    • abnormal olfactory bulb development (MGI Ref ID J:38857)
      • internal plexiform layer between mitral cell layer and internal granule layers is absent
    • abnormal striatum morphology (MGI Ref ID J:38857)
      • size is reduced
    • abnormal subplate morphology (MGI Ref ID J:71181)
      • at E18.5, an ectopic cortical subplate is detected under the most superficial cortical plate with later-born cortical neurons accumulated underneath
    • decreased corpus callosum size (MGI Ref ID J:38857)
      • size (thickness) is significantly reduced
    • dilated lateral ventricles (MGI Ref ID J:38857)
      • lateral ventricles are ~twice the size of lateral ventricles in wild type brain in 3-month old animals
    • thin cortical plate (MGI Ref ID J:38857)
      • cortical plate is 30-50% thinner than in wild-type embryos at E15
  • ectopic Purkinje cell (MGI Ref ID J:38857)
    • some cells are located in granule cell layer
  • seizures (MGI Ref ID J:38857)
    • over long-term observation, seizures are observed
    • susceptibility to pharmacologically induced seizures (MGI Ref ID J:38857)
      • administration of 50 mg/kg pentylenetetrazol, induces generalized convulsions (with loss of posture, myclonic jerks, hyperextension of neck and trunk associated with cycling motions of limbs and extension of hind limbs) in wild-type and mutant mice with similar frequency, but slightly shorter latency in mutants; >50% of mutants die within minutes of end of tonic-clonic phase of seizures, whereas no wild-type animals die
  • behavior/neurological phenotype
  • seizures (MGI Ref ID J:38857)
    • over long-term observation, seizures are observed
    • susceptibility to pharmacologically induced seizures (MGI Ref ID J:38857)
      • administration of 50 mg/kg pentylenetetrazol, induces generalized convulsions (with loss of posture, myclonic jerks, hyperextension of neck and trunk associated with cycling motions of limbs and extension of hind limbs) in wild-type and mutant mice with similar frequency, but slightly shorter latency in mutants; >50% of mutants die within minutes of end of tonic-clonic phase of seizures, whereas no wild-type animals die
  • homeostasis/metabolism phenotype
  • susceptibility to pharmacologically induced seizures (MGI Ref ID J:38857)
    • administration of 50 mg/kg pentylenetetrazol, induces generalized convulsions (with loss of posture, myclonic jerks, hyperextension of neck and trunk associated with cycling motions of limbs and extension of hind limbs) in wild-type and mutant mice with similar frequency, but slightly shorter latency in mutants; >50% of mutants die within minutes of end of tonic-clonic phase of seizures, whereas no wild-type animals die

Cdk5r1tm1Lht/Cdk5r1tm1Lht

        involves: 129S4/SvJae
  • life span-post-weaning/aging
  • premature death (MGI Ref ID J:38857)
  • nervous system phenotype
  • abnormal cerebellar molecular layer (MGI Ref ID J:38857)
  • abnormal forebrain morphology (MGI Ref ID J:38857)
    • mice on 129 inbred background show the phenotypes observed on the mixed 129Sv/C57BL/6 background
    • abnormal cerebral cortex morphology (MGI Ref ID J:38857)
    • abnormal forebrain development (MGI Ref ID J:38857)
    • abnormal hippocampus morphology (MGI Ref ID J:38857)
      • abnormal dentate gyrus morphology (MGI Ref ID J:38857)
      • abnormal hippocampal laminar structure (MGI Ref ID J:38857)
    • abnormal olfactory bulb development (MGI Ref ID J:38857)
    • abnormal striatum morphology (MGI Ref ID J:38857)
    • decreased corpus callosum size (MGI Ref ID J:38857)
    • dilated lateral ventricles (MGI Ref ID J:38857)
  • ectopic Purkinje cell (MGI Ref ID J:38857)
  • seizures (MGI Ref ID J:38857)
  • behavior/neurological phenotype
  • seizures (MGI Ref ID J:38857)

Gene & Allele Details

Allele Symbol Cdk5r1tm1Lht
Allele Name targeted mutation 1, Li-Huei Tsai
Common Name(s) p35-;
Mutation Made By Li-Huei Tsai,   Harvard Medical School
Strain of Origin129S4/SvJae
ES Cell Line NameJ1
ES Cell Line Strain129S4/SvJae
Gene Symbol and Name Cdk5r1, cyclin-dependent kinase 5, regulatory subunit 1 (p35)
Chromosome 11
Gene Common Name(s) CDK5P35; CDK5R; D11Bwg0379e; DNA segment, Chr 11, Brigham & Women's Genetics 0379 expressed; MGC33831; NCK5A; p23; p25; p35; p35nck5a;
Molecular Note A neomycin resistance cassette replaced 1.4 kb of sequence, including the entire open reading frame. [MGI Ref ID J:38857]

Control Information

  Allele   Control
 Cdk5r1tm1Lht  000664 C57BL/6J
 
  Considerations for Choosing Controls

Genotyping Protocols

Cdk5r1tm1Lht

Colony Maintenance

Breeding & HusbandryThis strain originated on a B6;129S4 background and has been backcrossed to C57BL/6 for at least 5 generations.
Diet Information LabDiet® 5K52/5K67

Additional Web Information

Congenic Nomenclature
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Research Applications

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

Cdk5r1tm1Lht related

Neurobiology Research
Alzheimer's Disease
Behavioral and Learning Defects
Cerebellar Defects
Cortical Defects
Epilepsy
Neurodegeneration
Neurodevelopmental Defects
Neuromuscular Defects
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects

References

Selected Reference(s)

Chae T; Kwon YT; Bronson R; Dikkes P; Li E; Tsai LH. 1997. Mice lacking p35, a neuronal specific activator of Cdk5, display cortical lamination defects, seizures, and adult lethality. Neuron 18(1):29-42. [PubMed: 9010203]  [MGI Ref ID J:38857]

Additional References

Price and Supply Information

Strain Name: B6.129S4-Cdk5r1tm1Lht/J
Stock Number: 004163

Price Details

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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; Email: jaxservices@jax.org.
This strain is included in the Induced Mutant Resource Colony collection.

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Control InformationView Control Information in Strain Details.

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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.
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