Haploinsufficiency of X-linked intellectual disability gene CASK induces post-transcriptional changes in synaptic and cellular metabolic pathways.

Haploinsufficiency of X-linked intellectual disability gene CASK induces post-transcriptional changes in synaptic and cellular metabolic pathways. Exp Neurol. 2020 Apr 16;:113319 Authors: Patel PA, Liang C, Arora A, Vijayan S, Ahuja S, Wagley PK, Settlage R, Lew L, Goodkin HP, Lazar I, Srivastava S, Mukherjee K Abstract Heterozygous mutations in the X-linked gene CASK are associated with intellectual disability, microcephaly, pontocerebellar hypoplasia, optic nerve hypoplasia and partially penetrant seizures in girls. The Cask+/- heterozygous knockout female mouse phenocopies the human disorder and exhibits postnatal microencephaly, cerebellar hypoplasia and optic nerve hypoplasia. It is not known if Cask+/- mice also display seizures, nor is known the molecular mechanism by which CASK haploinsufficiency produces the numerous documented phenotypes. 24-h video electroencephalography demonstrates that despite sporadic seizure activity, the overall electrographic patterns remain unaltered in Cask+/- mice. Additionally, seizure threshold to the commonly used kindling agent, pentylenetetrazol, remains unaltered in Cask+/- mice, indicating that even in mice the seizure phenotype is only partially penetrant and may have an indirect mechanism. RNA sequencing experiments on Cask+/- mouse brain uncovers a very limited number of changes, with most differences arising in the transcripts of extracellular matrix proteins and the transcripts of a g...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research