Targeted mutation of the calbindin D<sub>28K</sub> gene disrupts circadian rhythmicity and entrainment

Kriegsfeld, Lance J.; Mei, Dan; Yan, Lily; Witkovsky, Paul; LeSauter, Joseph; Hamada, Toshiyuki; Silver, Rae

doi:10.1111/j.1460-9568.2008.06447.x

Cited by 15 publications

(39 citation statements)

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“…We found that Calb1 −/− mice display normal circadian rhythmicity, with period length, total activity, and activity distribution comparable to wild-type animals (see Figure 2). These findings differ from a previous report in which 40% of Calb1 −/− mice were described as arrhythmic and the other 60% showing low-amplitude circadian rhythmicity and marked activity during the subjective day (Kriegsfeld et al, 2008). Furthermore, in the latter group with low rhythmicity, no significant differences in phase shifting were observed between wild-type and Calb1 −/− mice at all the time points investigated (CT4, CT16, CT22).…”

Section: Discussioncontrasting

confidence: 99%

“…However, at CT10 and CT22, which correspond to the subjective day and phase-advance portion of the phase-response curve, respectively, no difference between Calb1 −/− and wild-type mice is observed (see Figure 3), suggesting the phase-response curve is unlikely to be shifted. These findings reinforce previous observations that indicated a tendency for slightly larger phase delays in Calb1 −/− mice (Kriegsfeld et al, 2008), although in that study, CT16 was investigated for phase delays in contrast to CT14 in our study. Comparable to the results in mice, a role for CB in phase shifting was observed in hamsters (LeSauter et al, 1999).…”

Section: Discussionsupporting

confidence: 93%

“…They were then back-crossed for eight generations to B6 mice in Fribourg, Switzerland, and Calb1 +/-siblings were used to generate wild-type and Calb1 −/− littermates. Thus, the most likely explanation for the discrepancy between the results of the study by Kriegsfeld et al (2008) and ours lies in subtle genetic differences between the two theoretically "identical" Calb1 −/− strains. CB expressing neurons in the SCN of hamsters receive direct input from the retina via the retinohypothalamic tract (Bryant et al, 2000).…”

Section: Discussioncontrasting

confidence: 86%

“…The original mutation (Airaksinen et al, 1997) was made in embryonic stem cells of the 129 strain. Kriegsfeld et al (2008) consider it rather unlikely that in their back-crossed strain (for seven generations to B6) that the region flanking the targeted Calb1 gene, which most likely maintains some of the Sv129 alleles, is responsible for the observed effects. Animals used in our study are derived from the initial Calb1 −/− mice generated by Airaksinen et al (1997) with a mixed R1 × B6 genetic background.…”

Section: Discussionmentioning

confidence: 99%

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Lack of Calbindin-D28k Alters Response of the Murine Circadian Clock to Light

Stadler

Schmutz

Schwaller

et al. 2010

Chronobiology International

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A strong stimulus adjusting the circadian clock to the prevailing light-dark cycle is light. However, the circadian clock is reset by light only at specific times of the day. The mechanisms mediating such gating of light input to the CNS are not well understood. There is evidence that Ca 2+ ions play an important role in intracellular signaling mechanisms, including signaling cascades stimulated by light. Therefore, Ca 2+ is hypothesized to play a role in the light-mediated resetting of the circadian clock. Calbindin-D28k (CB; gene symbol: Calb1) is a Ca 2+ binding protein implicated in Ca 2+ homeostasis and sensing. The absence of this protein influences Ca 2+ buffering capacity of a cell, alters spatio-temporal aspects of intracellular Ca 2+ signaling, and hence might alter transmission of light information to the circadian clock in neurons of the suprachiasmatic nuclei (SCN). We tested mice lacking a functional Calb1 gene (Calb1 −/−) and found an increased phase-delay response to light applied at circadian time (CT) 14 in these animals. This is accompanied by elevated induction of Per2 gene expression in the SCN. Period length and circadian rhythmicity were comparable between Calb1 −/− and wild-type animals. Our findings indicate an involvement of CB in the signaling pathway that modulates the behavioral and molecular response to light.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Lack of Calbindin-D28k Alters Response of the Murine Circadian Clock to Light

Stadler

Schmutz

Schwaller

et al. 2010

Chronobiology International

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“…The numbers of synapses and astrocytes increase rapidly during the early developmental period, and apoptotic neuronal death occurs in the SCN from the late embryonic days through postnatal day 6 (P6) (refs 18,19). Furthermore, immunostained calcium-binding protein in the SCN decreases during the postnatal period 20 . These changes may influence the cell networks of the SCN, and alter the cellular couplings for rhythm synchrony.…”

mentioning

confidence: 96%

Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus

2013

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Cryptochrome (Cry) 1 and Cry2 are regarded as critical components for circadian rhythm generation in mammals. Nevertheless, cultured suprachiasmatic nucleus (SCN) of neonatal Cry double deficient (Cry1 À / À /Cry2 À / À ) mice exhibit circadian rhythms that damp out in several cycles. Here, by combining bioluminescence imaging of Per1-luc and PER2::LUC with multielectrode recording, we show developmental changes in SCN circadian rhythms in Cry1 À / À /Cry2 À / À mice. At the tissue level, circadian rhythms are found in neonatal but not in adult SCN, whereas at the cellular level, rhythms are detected in both SCN. Cellular circadian rhythms are synchronized in neonates, but not in adults, indicating a loss of rhythm synchrony in the course of development. Synchronized circadian rhythms in adult Cry1 À / À / Cry2 À / À SCN are restored by coculture of neonatal, but not of juvenile, SCN. These findings indicate that CRY1 and CRY2 are necessary for the development of intercellular networks that subserve coherent rhythm expression in adult SCN.

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Specializations of gastrin‐releasing peptide cells of the mouse suprachiasmatic nucleus

Drouyer

LeSauter

Hernandez

et al. 2010

J of Comparative Neurology

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The suprachiasmatic nucleus (SCN) of the hypothalamus regulates daily rhythms in physiology and behavior. It is constituted of a heterogeneous population of cells which together form the circuits underlying its master clock function. Numerous studies suggest the existence of two regions that have been termed core and shell. At a gross level, differences between these regions map to distinct functional differences, though the specific role(s) of various peptidergic cellular phenotypes remains unknown. In mouse, gastrin releasing peptide (GRP) cells lie in the core, are directly retinorecipient and lack detectable rhythmicity in clock gene expression, raising interest in their role in the SCN. Here, we provide evidence that calbindin expressing cells of perinatal mouse SCN express GRP, identified by a green fluorescent protein (GFP+), but lack detectable calbindin later in development. To explore the intra-SCN network in which GRP neurons participate, individual GFP+ cells were filled with tracer and their morphological characteristics, processes, and connections, as well as those of their non-GFP containing immediate neighbors, were compared. The results show that GFP+ neurons form a dense network of local circuits within the core, revealed by appositions on other GFP + cells and by the presence of dye-coupled cells. Dendrites and axons of GFP+ cells make appositions on arginine vasopressin neurons, while non-GFP cells have a less extensive fiber network, largely confined to the region of GFP+ cells. The results point to specialized circuitry within the SCN, presumably supporting synchronization of neural activity and reciprocal communication between core and shell regions.

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Targeted mutation of the calbindin D_28K gene disrupts circadian rhythmicity and entrainment

Cited by 15 publications

References 2 publications

Lack of Calbindin-D28k Alters Response of the Murine Circadian Clock to Light

Lack of Calbindin-D28k Alters Response of the Murine Circadian Clock to Light

Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus

Specializations of gastrin‐releasing peptide cells of the mouse suprachiasmatic nucleus

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Targeted mutation of the calbindin D28K gene disrupts circadian rhythmicity and entrainment

Cited by 15 publications

References 2 publications

Lack of Calbindin-D28k Alters Response of the Murine Circadian Clock to Light

Lack of Calbindin-D28k Alters Response of the Murine Circadian Clock to Light

Cryptochromes are critical for the development of coherent circadian rhythms in the mouse suprachiasmatic nucleus

Specializations of gastrin‐releasing peptide cells of the mouse suprachiasmatic nucleus

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Product

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Targeted mutation of the calbindin D_28K gene disrupts circadian rhythmicity and entrainment