Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Background Strain C57BL/6 Donor Strain 129x1 x 129S1 via R1 (+Kitl-SlJ) ES cell line Generation N5F8N1p   Donating Investigator Michael Meyer,   Ludwig-Maximilians-University Munich

Appearance
black, ataxic
Related Genotype: a/a Calb1^tm1Mpin/Calb 1^tm1Mpin

Description
Mice homozygous for the Calb1^tm1Mpin targeted mutation are viable and fertile. Homozygous mutant mice show severe impairment in tests of motor coordination and exhibit ataxia when challenged on a runway. These results suggest functional deficits in cerebellar pathways. Confocal calcium imaging of cerebellar Purkinje cells reveals marked changes of synaptically-evoked postsynaptic calcium transients.

Control Information

	Control
	000664 C57BL/6J
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

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

Calb1^tm1Mpin/Calb1⁺

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6

• behavior/neurological phenotype
• ataxia (MGI Ref ID J:38599)
  • 2-month old heterozygotes show significant deficits in initial trials in a thin horizontal rod test compared to controls but are significantly better than homozygotes; after first 2 sessions, no significant difference remains between mutant groups
• nervous system phenotype
• abnormal nervous system electrophysiology (MGI Ref ID J:38599)
  • heterozygotes show a significant increase in dendritic calcium transients upon climbing fiber stimulation compared to controls

Calb1^tm1Mpin/Calb1^tm1Mpin

        involves: 129S1/Sv * 129X1/SvJ * C57BL/6

• behavior/neurological phenotype
• ataxia (MGI Ref ID J:38599)
  • mutants do not display ataxia in standard environments; when challenged (with a runway test or rotarod test) coordination is severely disturbed compared to controls
  • mice display a shaky tremor which usually worsens during movement; controls do not show any tremors
• nervous system phenotype
• abnormal nervous system electrophysiology (MGI Ref ID J:38599)
  • dendritic calcium transients associated with complex spikes (synaptic response) upon climbing fiber stimulation is altered in mutants compared to controls; peak amplitudes are enhanced by ~80% over wild-type
• hearing/vestibular/ear phenotype
• *normal* hearing/vestibular/ear phenotype (MGI Ref ID J:60520)
  • at 4-8 months, homozygotes exhibit normal cochlear morphology, as well as normal hearing and cochlear OHC function, as assessed by baseline auditory brainstem evoked responses and DPOAEs, respectively
  • at 3 weeks after exposure to a moderate noise trauma, homozygotes exhibit a similar loss of cochlear hair cells to wild-type mice, with no significant differences in permanent threshold shifts of ABR or DPOAE amplitudes

View Research Applications

Research Applications

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

Calb1^tm1Mpin related

Apoptosis Research
Endogenous Regulators

Metabolism Research

Neurobiology Research
Ataxia (Movement) Defects
Cerebellar Defects
Metabolic Defects
Neurodegeneration

Genes & Alleles

Gene & Allele Information

Allele Symbol		Calb1tm1Mpin
Allele Name		targeted mutation 1, Max-Planck-Institute for Neurobiology
Allele Type		Targeted (knock-out)
Common Name(s)		CaBP-; Cb-; calbindin D28K -;
Mutation Made By		Michael Meyer,   Ludwig-Maximilians-University Munich
Strain of Origin		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
ES Cell Line Name		R1
ES Cell Line Strain		(129X1/SvJ x 129S1/Sv)F1-Kitl<+>
Gene Symbol and Name		Calb1, calbindin 1
Chromosome		4
Gene Common Name(s)		Brain-2; CALB; CB; CaBP28K; Calb; Calb-1; MGC93326; calbindin-D28K;
Molecular Note		A genomic fragment containing the promoter and first exon was replaced with a neomycin selection cassette. Western blot and immunohistochemistry analysis on tissues derived from homozygous mice demonstrated that no detectable protein was produced from this allele. [MGI Ref ID J:38599]

Genotyping

Genotyping Information

Genotyping Protocols

Calb1^tm1Mpin, SEP PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Additional References

Airaksinen MS; Thoenen H; Meyer M. 1997. Vulnerability of midbrain dopaminergic neurons in calbindin-D28k-deficient mice: lack of evidence for a neuroprotective role of endogenous calbindin in MPTP-treated and weaver mice. Eur J Neurosci 9(1):120-7. [PubMed: 9042576]  [MGI Ref ID J:40696]

Fletcher C; Norman DJ; Heintz N. 1991. Genetic mapping of meander tail, a mouse mutation affecting cerebellar development. Genomics 9(4):647-55. [PubMed: 2037292]  [MGI Ref ID J:11192]

Frantz GD; Tobin AJ. 1994. Cellular distribution of calbindin D28K mRNAs in the adult mouse brain. J Neurosci Res 37(3):287-302. [PubMed: 8176753]  [MGI Ref ID J:16904]

Schiffmann SN; Cheron G; Lohof A; d'Alcantara P; Meyer M; Parmentier M; Schurmans S. 1999. Impaired motor coordination and Purkinje cell excitability in mice lacking calretinin. Proc Natl Acad Sci U S A 96(9):5257-62. [PubMed: 10220453]  [MGI Ref ID J:54517]

Sooy K; Schermerhorn T; Noda M; Surana M; Rhoten WB; Meyer M; Fleischer N; Sharp GW; Christakos S. 1999. Calbindin-D(28k) controls [Ca(2+)](i) and insulin release. Evidence obtained from calbindin-d(28k) knockout mice and beta cell lines. J Biol Chem 274(48):34343-9. [PubMed: 10567411]  [MGI Ref ID J:58854]

Calb1^tm1Mpin related

Airaksinen L; Virkkala J; Aarnisalo A; Meyer M; Ylikoski J; Airaksinen MS. 2000. Lack of calbindin-D28k does not affect hearing level or survival of hair cells in acoustic trauma. ORL J Otorhinolaryngol Relat Spec 62(1):9-12. [PubMed: 10654311]  [MGI Ref ID J:60520]

Airaksinen MS; Eilers J; Garaschuk O; Thoenen H; Konnerth A; Meyer M. 1997. Ataxia and altered dendritic calcium signaling in mice carrying a targeted null mutation of the calbindin D28k gene. Proc Natl Acad Sci U S A 94(4):1488-93. [PubMed: 9037080]  [MGI Ref ID J:38599]

Airaksinen MS; Thoenen H; Meyer M. 1997. Vulnerability of midbrain dopaminergic neurons in calbindin-D28k-deficient mice: lack of evidence for a neuroprotective role of endogenous calbindin in MPTP-treated and weaver mice. Eur J Neurosci 9(1):120-7. [PubMed: 9042576]  [MGI Ref ID J:40696]

Bouilleret V; Schwaller B; Schurmans S; Celio MR; Fritschy JM. 2000. Neurodegenerative and morphogenic changes in a mouse model of temporal lobe epilepsy do not depend on the expression of the calcium-binding proteins parvalbumin, calbindin, or calretinin Neuroscience 97(1):47-58. [PubMed: 10771338]  [MGI Ref ID J:62357]

Bouslama-Oueghlani L; Wehrle R; Sotelo C; Dusart I. 2003. The developmental loss of the ability of Purkinje cells to regenerate their axons occurs in the absence of myelin: an in vitro model to prevent myelination. J Neurosci 23(23):8318-29. [PubMed: 12967994]  [MGI Ref ID J:85604]

Chen G; Racay P; Bichet S; Celio MR; Eggli P; Schwaller B. 2006. Deficiency in parvalbumin, but not in calbindin D-28k upregulates mitochondrial volume and decreases smooth endoplasmic reticulum surface selectively in a peripheral, subplasmalemmal region in the soma of Purkinje cells. Neuroscience 142(1):97-105. [PubMed: 16860487]  [MGI Ref ID J:113147]

Cheron G; Gall D; Servais L; Dan B; Maex R; Schiffmann SN. 2004. Inactivation of calcium-binding protein genes induces 160 Hz oscillations in the cerebellar cortex of alert mice. J Neurosci 24(2):434-41. [PubMed: 14724241]  [MGI Ref ID J:87450]

Gkika D; Hsu YJ; van der Kemp AW; Christakos S; Bindels RJ; Hoenderop JG. 2006. Critical role of the epithelial Ca2+ channel TRPV5 in active Ca2+ reabsorption as revealed by TRPV5/calbindin-D28K knockout mice. J Am Soc Nephrol 17(11):3020-7. [PubMed: 17005931]  [MGI Ref ID J:135840]

Kriegsfeld LJ; Mei DF; Yan L; Witkovsky P; Lesauter J; Hamada T; Silver R. 2008. Targeted mutation of the calbindin D28K gene disrupts circadian rhythmicity and entrainment. Eur J Neurosci 27(11):2907-21. [PubMed: 18588531]  [MGI Ref ID J:137158]

Lalonde R; Strazielle C. 2007. Spontaneous and induced mouse mutations with cerebellar dysfunctions: behavior and neurochemistry. Brain Res 1140:51-74. [PubMed: 16499884]  [MGI Ref ID J:120621]

Muller A; Kukley M; Uebachs M; Beck H; Dietrich D. 2007. Nanodomains of single Ca2+ channels contribute to action potential repolarization in cortical neurons. J Neurosci 27(3):483-95. [PubMed: 17234581]  [MGI Ref ID J:117436]

Servais L; Bearzatto B; Schwaller B; Dumont M; De Saedeleer C; Dan B; Barski JJ; Schiffmann SN; Cheron G. 2005. Mono- and dual-frequency fast cerebellar oscillation in mice lacking parvalbumin and/or calbindin D-28k. Eur J Neurosci 22(4):861-70. [PubMed: 16115209]  [MGI Ref ID J:100990]

Servais L; Cheron G. 2005. Purkinje cell rhythmicity and synchronicity during modulation of fast cerebellar oscillation. Neuroscience 134(4):1247-59. [PubMed: 16054763]  [MGI Ref ID J:104422]

Sooy K; Schermerhorn T; Noda M; Surana M; Rhoten WB; Meyer M; Fleischer N; Sharp GW; Christakos S. 1999. Calbindin-D(28k) controls [Ca(2+)](i) and insulin release. Evidence obtained from calbindin-d(28k) knockout mice and beta cell lines. J Biol Chem 274(48):34343-9. [PubMed: 10567411]  [MGI Ref ID J:58854]

Turnbull CI; Looi K; Mangum JE; Meyer M; Sayer RJ; Hubbard MJ. 2004. Calbindin independence of calcium transport in developing teeth contradicts the calcium ferry dogma. J Biol Chem 279(53):55850-4. [PubMed: 15494408]  [MGI Ref ID J:95037]

Vecellio M; Schwaller B; Meyer M; Hunziker W; Celio MR. 2000. Alterations in Purkinje cell spines of calbindin D-28 k and parvalbumin knock-out mice. Eur J Neurosci 12(3):945-54. [PubMed: 10762324]  [MGI Ref ID J:89904]

Westerink RH; Rook MB; Beekwilder JP; Wadman WJ. 2006. Dual role of calbindin-D28K in vesicular catecholamine release from mouse chromaffin cells. J Neurochem 99(2):628-40. [PubMed: 16824046]  [MGI Ref ID J:119287]

Zheng W; Xie Y; Li G; Kong J; Feng JQ; Li YC. 2004. Critical role of calbindin-D28k in calcium homeostasis revealed by mice lacking both vitamin D receptor and calbindin-D28k. J Biol Chem 279(50):52406-13. [PubMed: 15456794]  [MGI Ref ID J:95170]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Purchasing information

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

Pricing

Supply Details

Standard Supply

Repository-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

	Control
	000664 C57BL/6J
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

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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.

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Fax: 207.288.6150
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phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (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 with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

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