Wwox p47T Partial Loss-Of-Function Mutation Induces Epilepsy, Progressive Neuroinflammation, and Cerebellar Degeneration in Mice Phenocopying Human SCAR12

Authors

Tabish Hussain
Kevin Sanchez
Jennifer Crayton
Dhurjhoti Saha
Collene Jeter
Yue Lu
Martin Abba
Ryan Seo
Jeffrey L Noebels
Laura Fonken
C Marcelo Aldaz

Publication Date

4-1-2023

Journal

Progress in Neurobiology

Abstract

WWOX gene loss-of-function (LoF) has been associated with neuropathologies resulting in developmental, epileptic, and ataxic phenotypes of varying severity based on the level of WWOX dysfunction. WWOX gene biallelic germline variant p.Pro47Thr (P47T) has been causally associated with a new form of autosomal recessive cerebellar ataxia with epilepsy and intellectual disability (SCAR12, MIM:614322). This mutation affecting the WW1 protein binding domain of WWOX, impairs its interaction with canonical proline-proline-X-tyrosine motifs in partner proteins. We generated a mutant knock-in mouse model of Wwox P47T mutation that phenocopies human SCAR12. Wwox

Keywords

Humans, Mice, Animals, Neuroinflammatory Diseases, Epilepsy, Mutation, Cerebellar Diseases, Phenotype, Neurodegenerative Diseases, WW Domain-Containing Oxidoreductase, Tumor Suppressor Proteins

Comments

Supplementary Materials

PMID: 36828035