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Crybb2 coding for βB2-crystallin affects sensorimotor gating and hippocampal function.

Sun M, Hölter SM, Stepan J, Garrett L, Genius J, Kremmer E, Hrabě de Angelis M, Wurst W, Lie DC, Bally-Cuif L, Eder M, Rujescu D, Graw J - Mamm. Genome (2013)

Bottom Line: These results point to an important function of βB2-crystallin in the hippocampal network.They indicate pleiotropic effects of mutations in the Crybb2 gene, which previously had been considered to be specific to the ocular lens.Moreover, our results are the first to demonstrate that βB2-crystallin has a role in hippocampal function and behavioral phenotypes.

View Article: PubMed Central - PubMed

Affiliation: Institute of Developmental Genetics, Helmholtz Center Munich - National Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany.

ABSTRACT
βB2-crystallin (gene symbol: Crybb2/CRYBB2) was first described as a structural protein of the ocular lens. This gene, however, is also expressed in several regions of the mammalian brain, although its function in this organ remains entirely unknown. To unravel some aspects of its function in the brain, we combined behavioral, neuroanatomical, and physiological analyses in a novel Crybb2 mouse mutant, O377. Behavioral tests with male O377 mutants revealed altered sensorimotor gating, suggesting modified neuronal functions. Since these mouse mutants also displayed reduced hippocampal size, we concentrated further investigations on the hippocampus. Free intracellular Ca(2+) levels were increased and apoptosis was enhanced in the hippocampus of O377 mutants. Moreover, the expression of the gene encoding calpain 3 (gene symbol Capn3) was elevated and the expression of genes coding for the NMDA receptor subunits was downregulated. Additionally, the number of parvalbumin-positive interneurons was decreased in the hippocampus but not in the cortex of the mutants. High-speed voltage-sensitive dye imaging demonstrated an increased translation of input-to-output neuronal activity in the dentate gyrus of this Crybb2 mutant. These results point to an important function of βB2-crystallin in the hippocampal network. They indicate pleiotropic effects of mutations in the Crybb2 gene, which previously had been considered to be specific to the ocular lens. Moreover, our results are the first to demonstrate that βB2-crystallin has a role in hippocampal function and behavioral phenotypes. This model can now be further explored by future experiments.

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Behavioral analysis of male O377 mutant mice and wild-type littermate control mice (n = 5–10). a–c Spontaneous exploratory behavior in the open field. No differences in horizontal (a) or vertical (b) locomotor activity. d No difference in working memory as indicated by spontaneous alternation in the Y-maze. e, f Social investigation of the stimulus animal during the sample phase (first exposure) of the social discrimination test. fO377 mutants spent significantly more time in social investigation than control males. g There were significant differences in the acoustic startle curves of O377 mutants in comparison to littermate controls. h Increased PPI in O377 mutants. *p < 0.05; **p < 0.01; ***p < 0.001; +/+ versus −/−
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Fig1: Behavioral analysis of male O377 mutant mice and wild-type littermate control mice (n = 5–10). a–c Spontaneous exploratory behavior in the open field. No differences in horizontal (a) or vertical (b) locomotor activity. d No difference in working memory as indicated by spontaneous alternation in the Y-maze. e, f Social investigation of the stimulus animal during the sample phase (first exposure) of the social discrimination test. fO377 mutants spent significantly more time in social investigation than control males. g There were significant differences in the acoustic startle curves of O377 mutants in comparison to littermate controls. h Increased PPI in O377 mutants. *p < 0.05; **p < 0.01; ***p < 0.001; +/+ versus −/−

Mentions: The age of the mice was 9 weeks during the Open Field test, 11 weeks at the ASR/PPI measurement, 13–16 weeks during the social discrimination test, and 26 weeks during the Y-maze test. Data are reported as mean ± standard error of the mean (SEM) in bar or line graphs, or are individually shown in scatterplots with a horizontal line indicating the mean. Data were statistically analyzed by two-way analysis of variance (ANOVA) (Fig. 1g, h) or by unpaired Student’s t test (Fig. 1a–f). The chosen level of significance was p < 0.05.Fig. 1


Crybb2 coding for βB2-crystallin affects sensorimotor gating and hippocampal function.

Sun M, Hölter SM, Stepan J, Garrett L, Genius J, Kremmer E, Hrabě de Angelis M, Wurst W, Lie DC, Bally-Cuif L, Eder M, Rujescu D, Graw J - Mamm. Genome (2013)

Behavioral analysis of male O377 mutant mice and wild-type littermate control mice (n = 5–10). a–c Spontaneous exploratory behavior in the open field. No differences in horizontal (a) or vertical (b) locomotor activity. d No difference in working memory as indicated by spontaneous alternation in the Y-maze. e, f Social investigation of the stimulus animal during the sample phase (first exposure) of the social discrimination test. fO377 mutants spent significantly more time in social investigation than control males. g There were significant differences in the acoustic startle curves of O377 mutants in comparison to littermate controls. h Increased PPI in O377 mutants. *p < 0.05; **p < 0.01; ***p < 0.001; +/+ versus −/−
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3824278&req=5

Fig1: Behavioral analysis of male O377 mutant mice and wild-type littermate control mice (n = 5–10). a–c Spontaneous exploratory behavior in the open field. No differences in horizontal (a) or vertical (b) locomotor activity. d No difference in working memory as indicated by spontaneous alternation in the Y-maze. e, f Social investigation of the stimulus animal during the sample phase (first exposure) of the social discrimination test. fO377 mutants spent significantly more time in social investigation than control males. g There were significant differences in the acoustic startle curves of O377 mutants in comparison to littermate controls. h Increased PPI in O377 mutants. *p < 0.05; **p < 0.01; ***p < 0.001; +/+ versus −/−
Mentions: The age of the mice was 9 weeks during the Open Field test, 11 weeks at the ASR/PPI measurement, 13–16 weeks during the social discrimination test, and 26 weeks during the Y-maze test. Data are reported as mean ± standard error of the mean (SEM) in bar or line graphs, or are individually shown in scatterplots with a horizontal line indicating the mean. Data were statistically analyzed by two-way analysis of variance (ANOVA) (Fig. 1g, h) or by unpaired Student’s t test (Fig. 1a–f). The chosen level of significance was p < 0.05.Fig. 1

Bottom Line: These results point to an important function of βB2-crystallin in the hippocampal network.They indicate pleiotropic effects of mutations in the Crybb2 gene, which previously had been considered to be specific to the ocular lens.Moreover, our results are the first to demonstrate that βB2-crystallin has a role in hippocampal function and behavioral phenotypes.

View Article: PubMed Central - PubMed

Affiliation: Institute of Developmental Genetics, Helmholtz Center Munich - National Research Center for Environmental Health, Ingolstädter Landstrasse 1, 85764, Neuherberg, Germany.

ABSTRACT
βB2-crystallin (gene symbol: Crybb2/CRYBB2) was first described as a structural protein of the ocular lens. This gene, however, is also expressed in several regions of the mammalian brain, although its function in this organ remains entirely unknown. To unravel some aspects of its function in the brain, we combined behavioral, neuroanatomical, and physiological analyses in a novel Crybb2 mouse mutant, O377. Behavioral tests with male O377 mutants revealed altered sensorimotor gating, suggesting modified neuronal functions. Since these mouse mutants also displayed reduced hippocampal size, we concentrated further investigations on the hippocampus. Free intracellular Ca(2+) levels were increased and apoptosis was enhanced in the hippocampus of O377 mutants. Moreover, the expression of the gene encoding calpain 3 (gene symbol Capn3) was elevated and the expression of genes coding for the NMDA receptor subunits was downregulated. Additionally, the number of parvalbumin-positive interneurons was decreased in the hippocampus but not in the cortex of the mutants. High-speed voltage-sensitive dye imaging demonstrated an increased translation of input-to-output neuronal activity in the dentate gyrus of this Crybb2 mutant. These results point to an important function of βB2-crystallin in the hippocampal network. They indicate pleiotropic effects of mutations in the Crybb2 gene, which previously had been considered to be specific to the ocular lens. Moreover, our results are the first to demonstrate that βB2-crystallin has a role in hippocampal function and behavioral phenotypes. This model can now be further explored by future experiments.

Show MeSH
Related in: MedlinePlus