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Type Congenic; Mutant Stock; 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 Talal Chatila, Boston Children's Hospital Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. No gene product (mRNA or protein) is detected by RT-PCR or Western blot analysis. Synaptic plasticity, as assayed by long-term potentiation (LTP) and long-term depression (LTD), in mutant mice is deficient. Homozygotes exhibit diminished contextual and auditory fear memory. Cyclic AMP-responsive element binding protein (CREB) activation by fear conditioning is absent in the amygdala and decreased in the hippocampus. Thymocyte maturation is impaired. Both CD4+ and CD8+, single positive, thymocyte levels are reduced. This mutant mouse strain may be useful in studies examining learning and memory or related to thymocyte development.Development
A targeting vector containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to disrupt exon 3 and adjacent introns. The construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6 blastocysts.
| Control | ||
|---|---|---|
| See control note: | C57BL/6J mice (Stock No. 000664) may be used as controls. | |
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
View Mammalian Phenotype Terms
Mammalian Phenotype Terms provided by MGI
assigned by genotype
Camk4tm1Tch/Camk4tm1Tch
B6.129X1-Camk4tm1Tch
- behavior/neurological phenotype
- abnormal learning/memory/conditioning
- memory for increased vestibuloocular reflex gain is impaired compared to in wild-type mice regardless of spaced training (MGI Ref ID J:122984)
- however, vestibuloocular reflex, motor function and optokinetic reflex are normal and reduced training stimulus frequency rescues memory of increased vestibuloocular reflex gain (MGI Ref ID J:122984)
- decreased chemically-elicited antinociception
- mice exhibit less analgesic tolerance after chronic morphine treatment compared to wild-type mice (MGI Ref ID J:108062)
- skeleton phenotype
- abnormal bone remodeling
- LPS-induced bone erosion is reduced compared to in wild-type mice (MGI Ref ID J:129599)
- abnormal osteoclast differentiation
- osteoclastognesis induced by RANKL is suppressed unlike in wild-type mice (MGI Ref ID J:129599)
- decreased osteoclast cell number (MGI Ref ID J:129599)
- increased bone mineral density (MGI Ref ID J:129599)
- increased bone volume
- bone volume is increased compared to in wild-type mice (MGI Ref ID J:129599)
- nervous system phenotype
- abnormal inhibitory postsynaptic currents
- pre-exposure to morphine fails to abolish the morphine-induced decrease in inhibitory postsynaptic current as in wild-type mice (MGI Ref ID J:108062)
- immune system phenotype
- abnormal osteoclast differentiation
- osteoclastognesis induced by RANKL is suppressed unlike in wild-type mice (MGI Ref ID J:129599)
- decreased osteoclast cell number (MGI Ref ID J:129599)
- hematopoietic system phenotype
- abnormal osteoclast differentiation
- osteoclastognesis induced by RANKL is suppressed unlike in wild-type mice (MGI Ref ID J:129599)
- decreased osteoclast cell number (MGI Ref ID J:129599)
- integument phenotype
- decreased chemically-elicited antinociception
- mice exhibit less analgesic tolerance after chronic morphine treatment compared to wild-type mice (MGI Ref ID J:108062)
- cellular phenotype
- abnormal osteoclast differentiation
- osteoclastognesis induced by RANKL is suppressed unlike in wild-type mice (MGI Ref ID J:129599)
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Camk4tm1Tch/Camk4tm1Tch
involves: 129X1/SvJ * C57BL/6
- nervous system phenotype
- *normal* nervous system phenotype
- mice exhibit normal neuroanatomy (MGI Ref ID J:64210)
- abnormal Purkinje cell dendrite morphology
- Purkinje neuron dendritic arbors appear reduced compared to wild-type neurons in culture (MGI Ref ID J:64210)
- abnormal excitatory postsynaptic currents
- the frequency of miniature excitatory postsynaptic currents is reduced by 70% and the R input is increased by 250% compared to in wild-type mice (MGI Ref ID J:64210)
- reduced long term depression
- long term depression is impaired (MGI Ref ID J:64210)
- behavior/neurological phenotype
- *normal* behavior/neurological phenotype
- mice exhibit normal spatial memory (MGI Ref ID J:64210)
- abnormal locomotor activation
- while locomotion and sensorimotor functions are normal, mice take longer to initiate movement compared to wild-type mice (MGI Ref ID J:64210)
View Research Applications
Research Applications
This mouse can be used to support research in many areas including:Camk4tm1Tch related
Immunology, Inflammation and Autoimmunity Research
Immunodeficiency
T cell deficiency
Internal/Organ Research
Lymphoid Tissue Defects
T cell deficiency
Neurobiology Research
Behavioral and Learning Defects
| Allele Symbol | Camk4tm1Tch | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Talal A Chatila | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | CaMKIV/Gr KO; Camk4-; | ||
| Mutation Made By | Talal Chatila, Boston Children's Hospital | ||
| Strain of Origin | 129X1/SvJ | ||
| ES Cell Line Name | RW-4 | ||
| ES Cell Line Strain | 129X1/SvJ | ||
| Gene Symbol and Name | Camk4, calcium/calmodulin-dependent protein kinase IV | ||
| Chromosome | 18 | ||
| Gene Common Name(s) | A430110E23Rik; AI666733; Ca2+/calmodulin-dependent protein kinase type IV/Gr; CaMK IV; CaMK-GR; CaMKIV; CaMKIV/Gr; Ccdpk; D18Bwg0362e; DNA segment, Chr 18, Brigham & Women's Genetics 0362 expressed; IV; RATCCDPK; RIKEN cDNA A430110E23 gene; caMK; expressed sequence AI666733; | ||
| Molecular Note | The replacement of the third exon, which encodes the ATP binding site in the catalytic domain of the kinase, with a neomycin resistance gene rendered the enzyme catalytically inactive and prone to degradation. [MGI Ref ID J:64210] | ||
Genotyping Protocols
Camk4tm1Tch, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
Ho N; Liauw JA; Blaeser F; Wei F; Hanissian S; Muglia LM; Wozniak DF; Nardi A; Arvin KL; Holtzman DM; Linden DJ; Zhuo M; Muglia LJ; Chatila TA. 2000. Impaired synaptic plasticity and cAMP response element-binding protein activation in Ca2+/calmodulin-dependent protein kinase type IV/Gr-deficient mice. J Neurosci 20(17):6459-72. [PubMed: 10964952] [MGI Ref ID J:64210]
Raman V; Blaeser F; Ho N; Engle DL; Williams CB; Chatila TA. 2001. Requirement for Ca(2+)/Calmodulin-Dependent Kinase Type IV/Gr in Setting the Thymocyte Selection Threshold. J Immunol 167(11):6270-8. [PubMed: 11714790] [MGI Ref ID J:72830]
Camk4tm1Tch relatedBlaeser F; Toppari J; Heikinheimo M; Yan W; Wallace M; Ho N; Chatila TA. 2001. CaMKIV/Gr is dispensable for spermatogenesis and CREM-regulated transcription in male germ cells. Am J Physiol Endocrinol Metab 281(5):E931-7. [PubMed: 11595648] [MGI Ref ID J:72562]
Boyden ES; Katoh A; Pyle JL; Chatila TA; Tsien RW; Raymond JL. 2006. Selective engagement of plasticity mechanisms for motor memory storage. Neuron 51(6):823-34. [PubMed: 16982426] [MGI Ref ID J:122984]
Evankovich J; Zhang R; Cardinal JS; Zhang L; Chen J; Huang H; Beer-Stolz D; Billiar TR; Rosengart MR; Tsung A. 2012. Calcium/calmodulin-dependent protein kinase IV limits organ damage in hepatic ischemia-reperfusion injury through induction of autophagy. Am J Physiol Gastrointest Liver Physiol 303(2):G189-98. [PubMed: 22575222] [MGI Ref ID J:191365]
Ichinose K; Rauen T; Juang YT; Kis-Toth K; Mizui M; Koga T; Tsokos GC. 2011. Cutting edge: Calcium/Calmodulin-dependent protein kinase type IV is essential for mesangial cell proliferation and lupus nephritis. J Immunol 187(11):5500-4. [PubMed: 22031763] [MGI Ref ID J:179759]
Jackson KJ; Sanjakdar SS; Chen X; Damaj MI. 2012. Nicotine reward and affective nicotine withdrawal signs are attenuated in calcium/calmodulin-dependent protein kinase IV knockout mice. PLoS One 7(11):e51154. [PubMed: 23226481] [MGI Ref ID J:195688]
Ko SW; Jia Y; Xu H; Yim SJ; Jang DH; Lee YS; Zhao MG; Toyoda H; Wu LJ; Chatila T; Kaang BK; Zhuo M. 2006. Evidence for a role of CaMKIV in the development of opioid analgesic tolerance. Eur J Neurosci 23(8):2158-68. [PubMed: 16630062] [MGI Ref ID J:108062]
Koga T; Ichinose K; Mizui M; Crispin JC; Tsokos GC. 2012. Calcium/calmodulin-dependent protein kinase IV suppresses IL-2 production and regulatory T cell activity in lupus. J Immunol 189(7):3490-6. [PubMed: 22942433] [MGI Ref ID J:190549]
Raman V; Blaeser F; Ho N; Engle DL; Williams CB; Chatila TA. 2001. Requirement for Ca(2+)/Calmodulin-Dependent Kinase Type IV/Gr in Setting the Thymocyte Selection Threshold. J Immunol 167(11):6270-8. [PubMed: 11714790] [MGI Ref ID J:72830]
Sato K; Suematsu A; Nakashima T; Takemoto-Kimura S; Aoki K; Morishita Y; Asahara H; Ohya K; Yamaguchi A; Takai T; Kodama T; Chatila TA; Bito H; Takayanagi H. 2006. Regulation of osteoclast differentiation and function by the CaMK-CREB pathway. Nat Med 12(12):1410-6. [PubMed: 17128269] [MGI Ref ID J:129599]
Wang H; Fukushima H; Kida S; Zhuo M. 2009. Ca2+/calmodulin-dependent protein kinase IV links group I metabotropic glutamate receptors to fragile X mental retardation protein in cingulate cortex. J Biol Chem 284(28):18953-62. [PubMed: 19436069] [MGI Ref ID J:151259]
Wang H; Wu LJ; Zhang F; Zhuo M. 2008. Roles of calcium-stimulated adenylyl cyclase and calmodulin-dependent protein kinase IV in the regulation of FMRP by group I metabotropic glutamate receptors. J Neurosci 28(17):4385-97. [PubMed: 18434517] [MGI Ref ID J:134617]
Wei F; Qiu CS; Liauw J; Robinson DA; Ho N; Chatila T; Zhuo M. 2002. Calcium calmodulin-dependent protein kinase IV is required for fear memory. Nat Neurosci 5(6):573-9. [PubMed: 12006982] [MGI Ref ID J:76670]
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.
| Pricing for USA, Canada and Mexico shipping destinations |
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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 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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Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
| Control | ||
|---|---|---|
| See control note: | C57BL/6J mice (Stock No. 000664) may be used as controls. | |
| 000664 C57BL/6J | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
| phone: | 207-288-6470 |
| fax: | 207-288-6655 |
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