English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Open

Mutation in  CUL4B , which encodes a scaffold protein of the E3 ubiquitin ligase complex, has been found in patients with X-linked mental retardation (XLMR). However, early deletion of  Cul4b  in mice causes prenatal lethality, which has frustrated attempts to characterize the phenotypes  in vivo . In this report, we successfully rescued  Cul4b  mutant mice by crossing female mice in which exons 4–5 of  Cul4b  were flanked by loxP sequences with  Sox2-Cre  male mice. In  Cul4b -deficient ( Cul4b  Δ  /Y ) mice, no CUL4B protein was detected in any of the major organs, including the brain. In the hippocampus, the levels of CUL4A, CUL4B substrates (TOP1, β-catenin, cyclin E and WDR5) and neuronal markers (MAP2, tau-1, GAP-43, PSD95 and syn-1) were not sensitive to  Cul4b  deletion, whereas the number of parvalbumin (PV)-positive GABAergic interneurons was decreased in  Cul4b  Δ  /Y  mice, especially in the dentate gyrus (DG). Some dendritic features, including the complexity, diameter and spine density in the CA1 and DG hippocampal neurons, were also affected by  Cul4b  deletion. Together, the decrease in the number of PV-positive neurons and altered dendritic properties in  Cul4b  Δ  /Y  mice imply a reduction in inhibitory regulation and dendritic integration in the hippocampal neural circuit, which lead to increased epileptic susceptibility and spatial learning deficits. Our results identify  Cul4b  Δ  /Y  mice as a potential model for the non-syndromic model of XLMR that replicates the  CUL4B -associated MR and is valuable for the development of a therapeutic strategy for treating MR.

Rescue of the genetically engineered Cul4b mutant mouse as a potential model for human X-linked mental retardation