brd1 gene  (ClinGen Resource)

Journal: Scientific Reports

Article Title: Brain volumetric alterations accompanied with loss of striatal medium-sized spiny neurons and cortical parvalbumin expressing interneurons in Brd1 +/− mice

doi: 10.1038/s41598-018-34729-5

Figure Lengend Snippet: 3D MR imaging-based brain volumetric analysis.

Article Snippet: A mouse line heterozygous for a targeted deletion in the Brd1 gene was generated by TaconicArtemis GmbH (Cologne, Germany) on a congenic C57BL/6NTac genetic background as previously described .

Techniques: Imaging

Journal: Scientific Reports

Article Title: Brain volumetric alterations accompanied with loss of striatal medium-sized spiny neurons and cortical parvalbumin expressing interneurons in Brd1 +/− mice

doi: 10.1038/s41598-018-34729-5

Figure Lengend Snippet: Assessment of brain structural changes using 3D structural magnetic resonance imaging, cell-type specific expression analysis of striatal differentially expressed genes, and estimation of striatal volume and neuron numbers using stereology in Brd1 +/− and WT mice. ( a ) Coronal and sagittal MRI slices showing the nominally significant differences in absolute volume of subcortical structures between 15 weeks old Brd1 +/− (n = 10) and WT (n = 9) mice. The percentage change in brain structure volume is indicated by the color bar on the left. ( b ) Horizontal, sagittal and coronal MRI slices showing local deformations between the average of Brd1 +/− and WT mice within striatum. The percentage voxel-based change in volume is indicated by the color bar on the left. (Red color marks Brd1 +/− mice larger and blue color marks Brd1 +/− smaller). ( c ) Stereological estimate on CPu volume in histological samples from an independent batch of 15 weeks old mice, further supports a significant volume loss in Brd1 +/− (n = 6) compared to WT (n = 7) mice (t test, p = 0.0069). ( d ) A heat map of the correlation coefficient matrix for volumes in all brain regions, structures, and sub-structures in Brd1 +/− and WT mice. The color scale on the left side shows the strength of the correlation using white (no correlation), blue (negative correlation), and red (positive correlation). ( e ) Illustration of cortical surface showing the localization of groupwise differences in cortical thickness. Only uncorrected p values are presented. Top: t-map (red color marks Brd1 +/− mice thicker and blue color marks Brd1 +/− thinner). Bottom: t-map with threshold cutoff at p < 0.05. ( f ) Stereological estimation of total number of CPu neurons show a significant reduction in 15 weeks old Brd1 +/− (n = 6) compared to WT (n = 7) mice (t test, p = 0.012). White arrows points to neurons, whereas black arrow points to glia. ( g ) Cell specific expression analysis (CSEA) of DEGs identified in dorsal striatum of 8 weeks old Brd1 +/− mice. Black bars show the Fisher’s Exact Benjamini-Hochberg (BH) corrected p values (−log 10 (q value)) of overlap between DEGs and 27 broad and specific cell type gene sets (at CSEA specificity threshold set to 0.0001). Red bars show the relative contribution of downregulated DEGs to that significance. Enrichments were regarded as statistically significant at q < 0.05 as indicated by the red dotted line. ( h ) Log2 fold change in expression of mRNA markers of various striatal cell types. Red dotted line indicates groupwise mean for markers for D1+ and D2+ MSNs, respectively. The decrease in markers for D2+ MSNs was moderately larger than that for D1+ MSNs (t test, p = 0.008). *p < 0.05; **p < 0.01; ***p < 0.001.

Article Snippet: A mouse line heterozygous for a targeted deletion in the Brd1 gene was generated by TaconicArtemis GmbH (Cologne, Germany) on a congenic C57BL/6NTac genetic background as previously described .

Techniques: Magnetic Resonance Imaging, Expressing

Journal: Scientific Reports

Article Title: Brain volumetric alterations accompanied with loss of striatal medium-sized spiny neurons and cortical parvalbumin expressing interneurons in Brd1 +/− mice

doi: 10.1038/s41598-018-34729-5

Figure Lengend Snippet: Volumes and cell numbers in WT and Brd1 +/− mice.

Article Snippet: A mouse line heterozygous for a targeted deletion in the Brd1 gene was generated by TaconicArtemis GmbH (Cologne, Germany) on a congenic C57BL/6NTac genetic background as previously described .

Techniques:

Journal: Scientific Reports

Article Title: Brain volumetric alterations accompanied with loss of striatal medium-sized spiny neurons and cortical parvalbumin expressing interneurons in Brd1 +/− mice

doi: 10.1038/s41598-018-34729-5

Figure Lengend Snippet: Stereological estimation of difference in numbers of anterior cingulate cortex (aCC) neurons expressing parvalbumin and the lectin, Vicia Villosa Agglutinin, cell-type specific expression analysis of differentially expressed genes detected in aCC, and difference in expression of interneuron markers in cortex at three developmental stages between WT and Brd1 +/− mice. ( a ) Estimation of aCC neurons stained positive for PV+ and VVA+ in tissue sections from 8 weeks old Brd1 +/− (n = 6) and WT (n = 8) mice reveals a reduction in cells expressing PV (t test, p = 0.008), VVA (t test, p = 0.003) and both (t test, p = 0.0025) in Brd1 +/− mice. ( b ) Illustration of image sampling in aCC. 7 image z-stacks were acquired from each hemisphere in 4 different tissue sections per animal. Z-stacks were approximately distributed across cortical layers as illustrated above (3 stacks in layer I-III, 3 in layer V and 1 in layer VI). Reduced number of neurons is restricted to tissue corresponding to cortical layer V (2-way ANOVA, genotype effect, p < 0.001, post hoc test (layer V) p < 0.01). ( c ) Cell specific expression analysis (CSEA) of DEGs identified in aCC of 8 weeks old Brd1 +/− mice. For further details see legend to Fig. ( d ) Log2 fold change (Log 2 FC) in expression of interneuron markers between WT and Brd1 +/− mice in whole cortex (newborns (P0), n = 6 in each group, (red)), frontal cortex (juvenile (P21), n = 7 in each group, (blue)), and aCC (adolescent (P56–63), n = 10 in each group, (black)). **p < 0.01.

Article Snippet: A mouse line heterozygous for a targeted deletion in the Brd1 gene was generated by TaconicArtemis GmbH (Cologne, Germany) on a congenic C57BL/6NTac genetic background as previously described .

Techniques: Expressing, Staining, Sampling

Journal: Scientific Reports

Article Title: Brain volumetric alterations accompanied with loss of striatal medium-sized spiny neurons and cortical parvalbumin expressing interneurons in Brd1 +/− mice

doi: 10.1038/s41598-018-34729-5

Figure Lengend Snippet: Comparison of group mean difference in volume of subcortical structures in ENIGMA SZ samples and Brd1 +/− mice. # Marks structures in which mean groupwise volume differ significantly between SZ patients and controls. *Marks structures in which mean groupwise volume differ significantly between Brd1 +/− and WT mice. In mice, caudate and putamen are not anatomically distinct and are referred to as the caudate-putamen .

Article Snippet: A mouse line heterozygous for a targeted deletion in the Brd1 gene was generated by TaconicArtemis GmbH (Cologne, Germany) on a congenic C57BL/6NTac genetic background as previously described .

Techniques: Comparison