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Gene Review

Calb2  -  calbindin 2

Mus musculus

Synonyms: CR, Calretinin, calretinin
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Disease relevance of Calb2


Psychiatry related information on Calb2

  • There was also no overlap between calretinin and GR early postnatally (P8) or after physical activity or exposure to an enriched environment, both of which are potent neurogenic stimuli [6].

High impact information on Calb2

  • This reduction preferentially affects calretinin(+) (bipolar cells) and somatostatin(+) subtypes (for example, bitufted cells), whereas parvalbumin(+) subpopulations (basket cells and chandelier cells) seem to be unaffected [7].
  • Here we show that the recently identified zinc finger transcription factor Sp8 is expressed in neurogenic regions, which give rise to olfactory bulb interneurons at embryonic and postnatal time points and remains expressed in the calretinin-expressing and GABAergic/nondopaminergic interneurons of the glomerular layer [8].
  • In ERbeta(-/-) mice, calretinin expression was markedly lower than in WT mice in the hippocampus, thalamus, and amygdala both at E16.5 and at E18 [9].
  • Among these CR cell-specific genes, 25 genes, including the CR cell marker genes such as the reelin and calretinin genes, are selectively and highly expressed in both embryonic and postnatal CR cells [10].
  • The firing behavior of Purkinje cells is severely affected in Cr-/- alert mice, with alterations of simple spike firing rate, complex spike duration, and simple spike pause [11].

Biological context of Calb2


Anatomical context of Calb2


Associations of Calb2 with chemical compounds

  • BrdU/CR-labeled cells were negative for GABA and GABAA1 receptor, but early on expressed granule cell marker Prox-1 [12].
  • CR expression was detected as early as 1 day after labeling dividing cells with bromodeoxyuridine (BrdU), but not before [12].
  • CR- and CB-expressing cells were protected from death during the first 2 h of exposure to NMDA [14].
  • Expression of calcium binding proteins, calretinin and calbindin-D28K, normally widely seen in dorsal horn interneurons, was up-regulated on the DCP-treated side [20].
  • Expression of high levels of exogenous calbindin or calretinin decreased transcription mediated by PCE1 in Purkinje cells 2.5- to 3-fold, whereas the presence of 1 microM ionomycin in the extracellular medium increased expression [21].

Co-localisations of Calb2

  • Early after BrdU, CR colocalized with immature neuronal marker doublecortin; and later with persisting neuronal marker NeuN [12].

Regulatory relationships of Calb2


Other interactions of Calb2

  • Indeed, chronic exposure of cultured cortical neurons for 5 days to increasing concentrations of BDNF (0.1-10 ng/ml) resulted in a concentration-dependent decrease in the number of calretinin-positive neurons and a concentration-dependent increase in the number of calbindin-immunoreactive neurons [25].
  • Thus, our data show an important species difference in the chemical distinction of inhibitory neuron subtypes, and indicate that colocalization of CR in SST cells correlates with different morphological and physiological features [26].
  • However, calretinin- and calbindin-immunoreactive cells were not Pax-6 immunopositive [27].
  • Interestingly, calretinin immunoreactive neurons, which contribute a minor subpopulation, were not affected suggesting that neurotrophin-3 independent regulation of neurogenesis occurs in addition to prominent neurotrophin-3 dependent mechanisms [28].
  • We also found decreased calretinin labeling in Pemt-/- (down to 43% compared to wild-type mice; p<0.01) [15].

Analytical, diagnostic and therapeutic context of Calb2

  • CalR immunohistochemistry and bromo-deoxyuridine birthdating confirmed the abnormality in position of the earliest generated cortical cells of mutants [29].
  • We have generated Cr-deficient (Cr-/-) mice by gene targeting and have investigated the associated phenotype [30].
  • In this second study, we have combined two-photon calcium imaging with whole-cell recording and anatomic reconstructions to directly characterize synaptically evoked calcium signals in three types of mouse V1 supragranular interneurones: parvalbumin-positive fast spikers (FS), calretinin-positive irregular spikers (IS), and adapting cells (AD) [31].
  • Double immunofluorescence staining procedures were used for tyrosine hydroxylase (a dopaminergic cell marker) and Calbindin-D28k or calretinin [32].
  • Double immunofluorescence and confocal microscopy showed that mossy terminals of CR-positive (CR(+)) UBCs were immunoreactive for VGLUT1 and VGLUT2, while mossy terminals of mGluR1alpha-positive (mGluR1alpha(+)) UBCs were provided with VGLUT1 only [33].


  1. Severe, early and selective loss of a subpopulation of GABAergic inhibitory neurons in experimental transmissible spongiform encephalopathies. Guentchev, M., Groschup, M.H., Kordek, R., Liberski, P.P., Budka, H. Brain Pathol. (1998) [Pubmed]
  2. CCR7, CCR8, CCR9 and CCR10 in the mouse hippocampal CA1 area and the dentate gyrus during and after pilocarpine-induced status epilepticus. Liu, J.X., Cao, X., Tang, Y.C., Liu, Y., Tang, F.R. J. Neurochem. (2007) [Pubmed]
  3. Development of calretinin immunoreactivity in the mouse inner ear. Dechesne, C.J., Rabejac, D., Desmadryl, G. J. Comp. Neurol. (1994) [Pubmed]
  4. Targeted calretinin expression in granule cells of calretinin-null mice restores normal cerebellar functions. Bearzatto, B., Servais, L., Roussel, C., Gall, D., Baba-Aïssa, F., Schurmans, S., de Kerchove d'Exaerde, A., Cheron, G., Schiffmann, S.N. FASEB J. (2006) [Pubmed]
  5. Anticachectic effects of the natural herb Coptidis rhizoma and berberine on mice bearing colon 26/clone 20 adenocarcinoma. Iizuka, N., Hazama, S., Yoshimura, K., Yoshino, S., Tangoku, A., Miyamoto, K., Okita, K., Oka, M. Int. J. Cancer (2002) [Pubmed]
  6. Age-dependent expression of glucocorticoid- and mineralocorticoid receptors on neural precursor cell populations in the adult murine hippocampus. Garcia, A., Steiner, B., Kronenberg, G., Bick-Sander, A., Kempermann, G. Aging Cell (2004) [Pubmed]
  7. Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy. Cobos, I., Calcagnotto, M.E., Vilaythong, A.J., Thwin, M.T., Noebels, J.L., Baraban, S.C., Rubenstein, J.L. Nat. Neurosci. (2005) [Pubmed]
  8. The zinc finger transcription factor Sp8 regulates the generation and diversity of olfactory bulb interneurons. Waclaw, R.R., Allen, Z.J., Bell, S.M., Erdélyi, F., Szabó, G., Potter, S.S., Campbell, K. Neuron (2006) [Pubmed]
  9. Estrogen receptor beta expression in the embryonic brain regulates development of calretinin-immunoreactive GABAergic interneurons. Fan, X., Warner, M., Gustafsson, J.A. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  10. Distinct ontogenic and regional expressions of newly identified Cajal-Retzius cell-specific genes during neocorticogenesis. Yamazaki, H., Sekiguchi, M., Takamatsu, M., Tanabe, Y., Nakanishi, S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  11. Impaired motor coordination and Purkinje cell excitability in mice lacking calretinin. Schiffmann, S.N., Cheron, G., Lohof, A., d'Alcantara, P., Meyer, M., Parmentier, M., Schurmans, S. Proc. Natl. Acad. Sci. U.S.A. (1999) [Pubmed]
  12. Transient calretinin expression defines early postmitotic step of neuronal differentiation in adult hippocampal neurogenesis of mice. Brandt, M.D., Jessberger, S., Steiner, B., Kronenberg, G., Reuter, K., Bick-Sander, A., von der Behrens, W., Kempermann, G. Mol. Cell. Neurosci. (2003) [Pubmed]
  13. Calcium binding protein containing neurons in the gliotic mouse hippocampus with special reference to their afferents from the medial septum and the entorhinal cortex. Tang, F.R., Chia, S.C., Jiang, F.L., Ma, D.L., Chen, P.M., Tang, Y.C. Neuroscience (2006) [Pubmed]
  14. Calretinin and calbindin D-28k delay the onset of cell death after excitotoxic stimulation in transfected P19 cells. D'Orlando, C., Fellay, B., Schwaller, B., Salicio, V., Bloc, A., Gotzos, V., Celio, M.R. Brain Res. (2001) [Pubmed]
  15. Deletion of the Pemt gene increases progenitor cell mitosis, DNA and protein methylation and decreases calretinin expression in embryonic day 17 mouse hippocampus. Zhu, X., Mar, M.H., Song, J., Zeisel, S.H. Brain Res. Dev. Brain Res. (2004) [Pubmed]
  16. Age-related changes in calbindin D-28k and calretinin immunoreactivity in the inferior colliculus of CBA/CaJ and C57Bl/6 mice. Zettel, M.L., Frisina, R.D., Haider, S.E., O'Neill, W.E. J. Comp. Neurol. (1997) [Pubmed]
  17. Determination of retinal cell fates is affected in the absence of extraocular striated muscles. Kablar, B. Dev. Dyn. (2003) [Pubmed]
  18. Embryonic and postnatal development of GABA, calbindin, calretinin, and parvalbumin in the mouse claustral complex. Dávila, J.C., Real, M.A., Olmos, L., Legaz, I., Medina, L., Guirado, S. J. Comp. Neurol. (2005) [Pubmed]
  19. Development of neurons and fibers containing calcium binding proteins in the pallial amygdala of mouse, with special emphasis on those of the basolateral amygdalar complex. Legaz, I., Olmos, L., Real, M.A., Guirado, S., Dávila, J.C., Medina, L. J. Comp. Neurol. (2005) [Pubmed]
  20. Alteration of sensorineural circuits in spinal cord by chronic contact dermatitis. Seike, M., Hamada, R., Ikeda, M., Kodama, H. Somatosensory & motor research. (2005) [Pubmed]
  21. A calcium responsive element that regulates expression of two calcium binding proteins in Purkinje cells. Arnold, D.B., Heintz, N. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  22. Information provided by the skeletal muscle and associated neurons is necessary for proper brain development. Kablar, B., Rudnicki, M.A. Int. J. Dev. Neurosci. (2002) [Pubmed]
  23. Origins of cortical interneuron subtypes. Xu, Q., Cobos, I., De La Cruz, E., Rubenstein, J.L., Anderson, S.A. J. Neurosci. (2004) [Pubmed]
  24. Cortical interneuron fate determination: diverse sources for distinct subtypes? Xu, Q., de la Cruz, E., Anderson, S.A. Cereb. Cortex (2003) [Pubmed]
  25. Opposite regulation of calbindin and calretinin expression by brain-derived neurotrophic factor in cortical neurons. Fiumelli, H., Kiraly, M., Ambrus, A., Magistretti, P.J., Martin, J.L. J. Neurochem. (2000) [Pubmed]
  26. Mouse cortical inhibitory neuron type that coexpresses somatostatin and calretinin. Xu, X., Roby, K.D., Callaway, E.M. J. Comp. Neurol. (2006) [Pubmed]
  27. Olfactory bulb development is altered in small-eye (Sey) mice. Dellovade, T.L., Pfaff, D.W., Schwanzel-Fukuda, M. J. Comp. Neurol. (1998) [Pubmed]
  28. Most classes of dorsal root ganglion neurons are severely depleted but not absent in mice lacking neurotrophin-3. Airaksinen, M.S., Meyer, M. Neuroscience (1996) [Pubmed]
  29. Role of p35/Cdk5 in preplate splitting in the developing cerebral cortex. Rakić, S., Davis, C., Molnár, Z., Nikolić, M., Parnavelas, J.G. Cereb. Cortex (2006) [Pubmed]
  30. Impaired long-term potentiation induction in dentate gyrus of calretinin-deficient mice. Schurmans, S., Schiffmann, S.N., Gurden, H., Lemaire, M., Lipp, H.P., Schwam, V., Pochet, R., Imperato, A., Böhme, G.A., Parmentier, M. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  31. Ca2+ imaging of mouse neocortical interneurone dendrites: contribution of Ca2+-permeable AMPA and NMDA receptors to subthreshold Ca2+dynamics. Goldberg, J.H., Yuste, R., Tamas, G. J. Physiol. (Lond.) (2003) [Pubmed]
  32. Midbrain dopaminergic neurons in the mouse: co-localization with Calbindin-D28K and calretinin. Liang, C.L., Sinton, C.M., German, D.C. Neuroscience (1996) [Pubmed]
  33. Vesicular glutamate transporters VGLUT1 and VGLUT2 define two subsets of unipolar brush cells in organotypic cultures of mouse vestibulocerebellum. Nunzi, M.G., Russo, M., Mugnaini, E. Neuroscience (2003) [Pubmed]
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