Calcium binding protein (calbindin-D28k) gene expression in the developing and aging mouse cerebellum

Iacopino, Anthony M.; Rhoten, William B.; Christakos, Sylvia

doi:10.1016/0169-328x(90)90041-b

Cited by 90 publications

(38 citation statements)

References 41 publications

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“…Hippocampal Calb1 mRNA was predominantly expressed in the dentate gyrus and moderate levels were expressed in CA1 neurons. Expression in the CB was particularly robust when compared to other brain regions and, as reported in rats, was specifically confined to the Purkinje neurons [26,27,28]. These findings confirm earlier studies mapping the distribution of Calb1 expression in the rat brain [26,29,30,31,32], but the current study is the first to characterize Calb1 mRNA expression in both sexes of juvenile mouse brain.…”

Section: Resultssupporting

confidence: 81%

Sex Differences in the Cerebellum and Frontal Cortex: Roles of Estrogen Receptor Alpha and Sex Chromosome Genes

Abel¹,

Witt²,

Rissman³

2011

Neuroendocrinology

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Most neurobehavioral diseases are sexually dimorphic in their incidence, and sex differences in the brain may be key for understanding and treating these diseases. Calbindin (Calb) D28K is used as a biomarker for the well-studied sexually dimorphic nucleus, a hypothalamic structure that is larger in males than in females. In the current study weanling C56BL/6J mice were used to examine sex differences in the Calb protein and message focusing on regions outside of the hypothalamus. A robust sex difference was found in Calb in the frontal cortex (FC) and cerebellum (CB; specifically in Purkinje cells); mRNA and protein were higher in females than in males. Using 2 mouse lines, i.e. one with a complete deletion of estrogen receptor alpha (ERα) and the other with uncoupled gonads and sex chromosomes, we probed the mechanisms that underlie sexual dimorphisms. In the FC, deletion of ERα reduced Calb1 mRNA in females compared to males. In addition, females with XY sex chromosomes had levels of Calb1 equal to those of males. Thus, both ERα and the sex chromosome complement regulate Calb1 in the FC. In the CB, ERα knockout mice of both sexes had reduced Calb1 mRNA, yet sex differences were retained. However, the sex chromosome complement, regardless of gonadal sex, dictated Calb1 mRNA levels. Mice with XX chromosomes had significantly greater Calb1 than did XY mice. This is the first study demonstrating that sex chromosome genes are a driving force producing sex differences in the CB and FC, which are neuoranatomical regions involved in many normal functions and in neurobehavioral diseases.

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Section: Resultssupporting

confidence: 81%

Sex Differences in the Cerebellum and Frontal Cortex: Roles of Estrogen Receptor Alpha and Sex Chromosome Genes

Abel¹,

Witt²,

Rissman³

2011

Neuroendocrinology

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“…Transient calbindin expression has been observed during embryonic development (11). Adult expression patterns develop steadily, as described in detail for the cerebellum (12). There, calbindin mRNA and protein increase postnatally to peak after the second postnatal week.…”

mentioning

confidence: 87%

Ataxia and altered dendritic calcium signaling in mice carrying a targeted null mutation of the calbindin D28k gene

Airaksinen

Eilers

Garaschuk

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

370

337

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Intracellular calcium-binding proteins are abundantly expressed in many neuronal populations. Previous evidence suggests that calcium-binding proteins can modulate various neuronal properties, presumably by their action as calcium buffers. The importance of calcium-binding proteins for nervous system function in an intact integrated system is, however, less clear. To investigate the physiological role of a major endogenous calcium-binding protein, calbindin D28k (calbindin) in vivo, we have generated calbindin null mutant mice by gene targeting. Surprisingly, calbindin deficiency does not affect general parameters of development and behavior or the structure of the nervous system at the light microscopic level. Null mutants are, however, severely impaired in tests of motor coordination, suggesting functional deficits in cerebellar pathways. Purkinje neurons, the only efferent of the cerebellar cortex, and inferior olive neurons, the source of the climbing fiber afferent, have previously been shown to express calbindin. Correlated with this unusual type of ataxia, confocal calcium imaging of Purkinje cells in cerebellar slices revealed marked changes of synaptically evoked postsynaptic calcium transients. Their fast, but not their slow, decay component had larger amplitudes in null mutant than in wild-type mice. We conclude that endogenous calbindin is of crucial importance for integrated nervous system function.

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“…In this structure, the CAT mRNA signal was found in the Purkinje cells ( Figure 5D). This finding was validated by immunohistochemical staining for GS, CAT and calbindin, a marker for Purkinje neurons [51,52] ( Figures 5G-5I). Comparison with the staining pattern of the cerebellum of a non-transgenic Swiss mouse demonstrated that the anti-CAT antibody reacted specifically in the Purkinje cells of the cerebellum of a GSL7 mouse (Figures 5J and 5K).…”

Section: Localization Of Gs and Cat Mrnas In The Brains Of Gsl And Gsmentioning

confidence: 99%

“…Serial sections of the brains of adult GSL and non-transgenic mice of the Swiss strain were incubated with polyclonal antibodies against CAT (5h 3h Inc. ; dilution 1 : 500) and GS [14], and with monoclonal antibodies against calbindin (Sigma ; 1 : 200) as a marker for Purkinje neurons in the cerebellum [51,52]. To visualize the binding of the antibodies, the indirect unconjungated peroxidase\anti-peroxidase technique [53] was used.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Role of the 5′ enhancer of the glutamine synthetase gene in its organ-specific expression

Lie-Venema

Boer

Moorman

et al. 1997

Biochemical Journal

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In mammals, glutamine synthetase (GS) is expressed in a large number of organs, but the precise regulation of its expression is still obscure. Therefore a detailed analysis of the activity of the upstream regulatory element of the GS gene in the transcriptional regulation of its expression was carried out in transgenic mice carrying the chloramphenicol acetyltransferase (CAT) gene under the control of the upstream regulatory region of the GS gene. CAT and GS mRNA expression were compared in liver, epididymis, lung, adipocytes, testis, kidney, skeletal muscle and gastrointestinal tract, both quantitatively by ribonuclease-protection analysis and topographically by in situ hybridization. It was found that the upstream regulatory region is active with respect both to the level and to the topography of GS gene expression in liver, epididymis, gastrointestinal tract (stomach, small intestine and colon) and skeletal muscle. On the other hand, in the kidney, brain, adipocytes, spleen, lung and testis, GS gene expression is not or only partly regulated by the 5´ enhancer. A second enhancer, identified within the first intron, may regulate GS expression in the latter organs. Furthermore, CAT expression in the brain did not co-localize with that of GS, showing that the 5´ regulatory region of the GS gene does not direct its expression to the astrocytes.

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Calcium binding protein (calbindin-D28k) gene expression in the developing and aging mouse cerebellum

Cited by 90 publications

References 41 publications

Sex Differences in the Cerebellum and Frontal Cortex: Roles of Estrogen Receptor Alpha and Sex Chromosome Genes

Sex Differences in the Cerebellum and Frontal Cortex: Roles of Estrogen Receptor Alpha and Sex Chromosome Genes

Ataxia and altered dendritic calcium signaling in mice carrying a targeted null mutation of the calbindin D28k gene

Role of the 5′ enhancer of the glutamine synthetase gene in its organ-specific expression

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