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

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 Background Strain C57BL/6 Donor Strain 129x1 x 129S1 via R1 (+Kitl-SlJ) ES cell line Generation N5F8N1p Generation Definitions   Donating Investigator Dr. 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

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      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
  • 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   (MGI Ref ID J:38599)
• nervous system phenotype
• abnormal nervous system electrophysiology
  • heterozygotes show a significant increase in dendritic calcium transients upon climbing fiber stimulation compared to controls   (MGI Ref ID J:38599)

Calb1^tm1Mpin/Calb1^tm1Mpin

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

• behavior/neurological phenotype
• ataxia
  • mutants do not display ataxia in standard environments; when challenged (with a runway test or rotarod test) coordination is severely disturbed compared to controls   (MGI Ref ID J:38599)
  • mice display a shaky tremor which usually worsens during movement; controls do not show any tremors   (MGI Ref ID J:38599)
• nervous system phenotype
• abnormal nervous system electrophysiology
  • 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   (MGI Ref ID J:38599)
• hearing/vestibular/ear phenotype
• *normal* hearing/vestibular/ear phenotype
  • 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   (MGI Ref ID J:60520)
  • 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   (MGI Ref ID J:60520)

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 provided by MGI

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		Dr. 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; CalbindinD28K; calbindin; calbindin-D (28k); 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, Separated PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

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]

Butler MP; LeSauter J; Sichel AN; Silver R. 2011. Targeted mutation of the calbindin D 28k gene selectively alters nonvisual photosensitivity. Eur J Neurosci 33(12):2299-307. [PubMed: 21545657]  [MGI Ref ID J:176370]

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]

Farre-Castany MA; Schwaller B; Gregory P; Barski J; Mariethoz C; Eriksson JL; Tetko IV; Wolfer D; Celio MR; Schmutz I; Albrecht U; Villa AE. 2007. Differences in locomotor behavior revealed in mice deficient for the calcium-binding proteins parvalbumin, calbindin D-28k or both. Behav Brain Res 178(2):250-61. [PubMed: 17275105]  [MGI Ref ID J:141743]

Ghoumari AM; Wehrle R; De Zeeuw CI; Sotelo C; Dusart I. 2002. Inhibition of protein kinase C prevents Purkinje cell death but does not affect axonal regeneration. J Neurosci 22(9):3531-42. [PubMed: 11978830]  [MGI Ref ID J:166584]

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]

Margolis DS; Kim D; Szivek JA; Lai LW; Lien YH. 2006. Functionally improved bone in calbindin-D28k knockout mice. Bone 39(3):477-84. [PubMed: 16631426]  [MGI Ref ID J:144911]

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]

Stadler F; Schmutz I; Schwaller B; Albrecht U. 2010. Lack of calbindin-D28k alters response of the murine circadian clock to light. Chronobiol Int 27(1):68-82. [PubMed: 20205558]  [MGI Ref ID J:187060]

Sullivan PG; Bruce-Keller AJ; Rabchevsky AG; Christakos S; Clair DK; Mattson MP; Scheff SW. 1999. Exacerbation of damage and altered NF-kappaB activation in mice lacking tumor necrosis factor receptors after traumatic brain injury. J Neurosci 19(15):6248-56. [PubMed: 10414954]  [MGI Ref ID J:110921]

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; Beekwilder JP; Wadman WJ. 2012. Differential alterations of synaptic plasticity in dentate gyrus and CA1 hippocampal area of Calbindin-D28K knockout mice. Brain Res 1450:1-10. [PubMed: 22405690]  [MGI Ref ID J:183244]

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

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

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'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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