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- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Former Names B6.129S4-Cdk5rtm1Lht/J (Changed: 17-FEB-05 ) Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Donating Investigator Li-Huei Tsai, Massachusetts Institue of Technology 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.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.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
Related Strains
Alzheimer's Disease Models
View Alzheimer's Disease Models (108 strains)
Additional Web Information
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Phenotype
Phenotype Information
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
- mortality/aging
- premature death
- ~15% of homozygotes die by ~4 months, starting at about 3 weeks of age (MGI Ref ID J:38857)
- nervous system phenotype
- abnormal cerebellar molecular layer
- molecular layer shows a greater cell density than wild-type, and contains cells resembling granule cells (MGI Ref ID J:38857)
- abnormal forebrain morphology
- in three-month old mice, general disorganization of forebrain is apparent (MGI Ref ID J:38857)
- abnormal cerebral cortex morphology
- laminated structure is not apparent in 3-month old mice; defects in lamination are less severe in lateral-ventral region of cortex (MGI Ref ID J:38857)
- no recognizable pattern is observed for distribution of pyramidal, granule, and polymorphic cells in cortex (MGI Ref ID J:38857)
- mutant cortex contains aberrant fascicles in the neocortex and no fascicles are seen in the lateral-ventral portion of the cortex (MGI Ref ID J:38857)
- radial distribution of pyramidal neurons and their apical dendrites is not conspicuous like in wild-type brains (MGI Ref ID J:38857)
- cortex shows mild neuronal-positioning abnormalities (MGI Ref ID J:71181)
- abnormal cerebral cortex pyramidal cell morphology
- orientation of neuronal soma and direction of dendritic growth are altered; defect is more severe in medial neocortex (MGI Ref ID J:38857)
- 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 (MGI Ref ID J:71181)
- abnormal dentate gyrus morphology (MGI Ref ID J:38857)
- abnormal hippocampus layer morphology
- abnormal olfactory bulb development
- internal plexiform layer between mitral cell layer and internal granule layers is absent (MGI Ref ID J:38857)
- abnormal striatum morphology
- size is reduced (MGI Ref ID J:38857)
- abnormal subplate morphology
- at E18.5, an ectopic cortical subplate is detected under the most superficial cortical plate with later-born cortical neurons accumulated underneath (MGI Ref ID J:71181)
- decreased corpus callosum size
- size (thickness) is significantly reduced (MGI Ref ID J:38857)
- dilated lateral ventricles
- lateral ventricles are ~twice the size of lateral ventricles in wild-type brain in 3-month old animals (MGI Ref ID J:38857)
- thin cortical plate
- cortical plate is 30-50% thinner than in wild-type embryos at E15 (MGI Ref ID J:38857)
- ectopic Purkinje cell
- some cells are located in granule cell layer (MGI Ref ID J:38857)
- seizures
- over long-term observation, seizures are observed (MGI Ref ID J:38857)
- increased susceptibility to pharmacologically induced seizures
- 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 (MGI Ref ID J:38857)
- behavior/neurological phenotype
- seizures
- over long-term observation, seizures are observed (MGI Ref ID J:38857)
- increased susceptibility to pharmacologically induced seizures
- 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 (MGI Ref ID J:38857)
Cdk5r1tm1Lht/Cdk5r1tm1Lht
involves: 129S4/SvJae
- mortality/aging
- premature death (MGI Ref ID J:38857)
- nervous system phenotype
- abnormal axon outgrowth
- neurons fail to respond to BDNF treatment with increased spine density unlike wild-type cells (MGI Ref ID J:193542)
- abnormal cerebellar molecular layer (MGI Ref ID J:38857)
- abnormal forebrain morphology
- mice on 129 inbred background show the phenotypes observed on the mixed 129Sv/C57BL/6 background (MGI Ref ID J:38857)
- 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 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)
- reduced long term potentiation
- following application of BDNF (MGI Ref ID J:193542)
- seizures (MGI Ref ID J:38857)
- behavior/neurological phenotype
- seizures (MGI Ref ID J:38857)
- cellular phenotype
- abnormal axon outgrowth
- neurons fail to respond to BDNF treatment with increased spine density unlike wild-type cells (MGI Ref ID J:193542)
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
Neurotransmitter Receptor and Synaptic Vesicle Defects
Receptor Defects
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Cdk5r1tm1Lht | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Li-Huei Tsai | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | p35-; | ||
| Mutation Made By | Li-Huei Tsai, Massachusetts Institue of Technology | ||
| Strain of Origin | 129S4/SvJae | ||
| ES Cell Line Name | J1 | ||
| ES Cell Line Strain | 129S4/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; 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] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Cdk5r1tm1Lht, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
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
Cdk5r1tm1Lht relatedBeffert U; Weeber EJ; Morfini G; Ko J; Brady ST; Tsai LH; Sweatt JD; Herz J. 2004. Reelin and cyclin-dependent kinase 5-dependent signals cooperate in regulating neuronal migration and synaptic transmission. J Neurosci 24(8):1897-906. [PubMed: 14985430] [MGI Ref ID J:90122]
Bianchetta MJ; Lam TT; Jones SN; Morabito MA. 2011. Cyclin-dependent kinase 5 regulates PSD-95 ubiquitination in neurons. J Neurosci 31(33):12029-35. [PubMed: 21849563] [MGI Ref ID J:176050]
Fu WY; Chen Y; Sahin M; Zhao XS; Shi L; Bikoff JB; Lai KO; Yung WH; Fu AK; Greenberg ME; Ip NY. 2007. Cdk5 regulates EphA4-mediated dendritic spine retraction through an ephexin1-dependent mechanism. Nat Neurosci 10(1):67-76. [PubMed: 17143272] [MGI Ref ID J:117343]
Gupta A; Sanada K; Miyamoto DT; Rovelstad S; Nadarajah B; Pearlman AL; Brunstrom J; Tsai LH. 2003. Layering defect in p35 deficiency is linked to improper neuronal-glial interaction in radial migration. Nat Neurosci 6(12):1284-91. [PubMed: 14608361] [MGI Ref ID J:86637]
Jana M; Dasgupta S; Pal U; Pahan K. 2009. IL-12 p40 homodimer, the so-called biologically inactive molecule, induces nitric oxide synthase in microglia via IL-12R beta 1. Glia 57(14):1553-65. [PubMed: 19306359] [MGI Ref ID J:156200]
Ko J; Humbert S; Bronson RT; Takahashi S; Kulkarni AB; Li E; Tsai LH. 2001. p35 and p39 are essential for cyclin-dependent kinase 5 function during neurodevelopment. J Neurosci 21(17):6758-71. [PubMed: 11517264] [MGI Ref ID J:71181]
Krapacher FA; Mlewski EC; Ferreras S; Pisano V; Paolorossi M; Hansen C; Paglini G. 2010. Mice lacking p35 display hyperactivity and paradoxical response to psychostimulants. J Neurochem 114(1):203-14. [PubMed: 20403084] [MGI Ref ID J:161822]
Kwon YT; Gupta A; Zhou Y; Nikolic M; Tsai LH. 2000. Regulation of N-cadherin-mediated adhesion by the p35-Cdk5 kinase. Curr Biol 10(7):363-72. [PubMed: 10753743] [MGI Ref ID J:113919]
Kwon YT; Tsai LH. 1998. A novel disruption of cortical development in p35(-/-) mice distinct from reeler. J Comp Neurol 395(4):510-22. [PubMed: 9619503] [MGI Ref ID J:47754]
Kwon YT; Tsai LH; Crandall JE. 1999. Callosal axon guidance defects in p35(-/-) mice. J Comp Neurol 415(2):218-29. [PubMed: 10545161] [MGI Ref ID J:58359]
Lagace DC; Benavides DR; Kansy JW; Mapelli M; Greengard P; Bibb JA; Eisch AJ. 2008. Cdk5 is essential for adult hippocampal neurogenesis. Proc Natl Acad Sci U S A 105(47):18567-71. [PubMed: 19017796] [MGI Ref ID J:142213]
Lai KO; Wong AS; Cheung MC; Xu P; Liang Z; Lok KC; Xie H; Palko ME; Yung WH; Tessarollo L; Cheung ZH; Ip NY. 2012. TrkB phosphorylation by Cdk5 is required for activity-dependent structural plasticity and spatial memory. Nat Neurosci 15(11):1506-15. [PubMed: 23064382] [MGI Ref ID J:193542]
Patel LS; Wenzel HJ; Schwartzkroin PA. 2004. Physiological and morphological characterization of dentate granule cells in the p35 knock-out mouse hippocampus: evidence for an epileptic circuit. J Neurosci 24(41):9005-14. [PubMed: 15483119] [MGI Ref ID J:97261]
Patzke H; Maddineni U; Ayala R; Morabito M; Volker J; Dikkes P; Ahlijanian MK; Tsai LH. 2003. Partial rescue of the p35-/- brain phenotype by low expression of a neuronal-specific enolase p25 transgene. J Neurosci 23(7):2769-78. [PubMed: 12684463] [MGI Ref ID J:82824]
Rakic S; Davis C; Molnar Z; Nikolic M; Parnavelas JG. 2006. Role of p35/Cdk5 in preplate splitting in the developing cerebral cortex. Cereb Cortex 16 Suppl 1:i35-45. [PubMed: 16766706] [MGI Ref ID J:174487]
Rakic S; Yanagawa Y; Obata K; Faux C; Parnavelas JG; Nikolic M. 2009. Cortical interneurons require p35/Cdk5 for their migration and laminar organization. Cereb Cortex 19(8):1857-69. [PubMed: 19037081] [MGI Ref ID J:174050]
Tan SS; Kalloniatis M; Truong HT; Binder MD; Cate HS; Kilpatrick TJ; Hammond VE. 2009. Oligodendrocyte positioning in cerebral cortex is independent of projection neuron layering. Glia 57(9):1024-30. [PubMed: 19062175] [MGI Ref ID J:156212]
Wenzel HJ; Robbins CA; Tsai LH; Schwartzkroin PA. 2001. Abnormal morphological and functional organization of the hippocampus in a p35 mutant model of cortical dysplasia associated with spontaneous seizures. J Neurosci 21(3):983-98. [PubMed: 11157084] [MGI Ref ID J:77303]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.Colony Maintenance
Breeding & Husbandry This strain originated on a B6;129S4 background and has been backcrossed to C57BL/6 for at least 5 generations. Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2250.00 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.
Embryos
Price (US dollars $) Frozen Embryo $1600.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2925.00 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.
Embryos
Price (US dollars $) Frozen Embryo $2080.00 Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
- Cryopreserved Embryos
Available to most shipping destinations1
This strain is also available as cryopreserved embryos2. Orders for cryopreserved embryos may be placed with our Customer Service Department. Experienced technicians at The Jackson Laboratory have recovered frozen embryos of this strain successfully. We will provide you enough embryos to perform two embryo transfers. The Jackson Laboratory does not guarantee successful recovery at your facility. For complete information on purchasing embryos, please visit our Cryopreserved Embryos web page.
1 Shipments cannot be made to Australia due to Australian government import restrictions.
2 Embryos for most strains are cryopreserved at the two cell stage while some strains are cryopreserved at the eight cell stage. If this information is important to you, please contact Customer Service.- Cryorecovery - Standard.
Progeny testing is not required.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 11 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.Cryorecovery to establish a Dedicated Supply for greater quantities of mice.
Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Control Information
| Control | ||
|---|---|---|
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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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.Ordering Information
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For Licensing and Use Restrictions view the link(s) below:
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JAX® Mice, Products & Services Conditions of Use
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
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