A novel gene edited rat model of cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL).

ABSTRACT:

Background

Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CARASIL) is a rare hereditary cerebral small vessel disease associated with loss-of-function mutations in the High Temperature Requirement Serine Protease 1 (HTRA1). While previous mouse models have provided insight into the functions of HTRA1, they have incompletely replicated the pathogenesis of CARASIL.

Methods

A novel gene-edited rat model of CARASIL (designated CRHTRA1) was generated containing the loss-of-function Htra1 mutation p.R302Q. Quantitative cognitive, physiological, pathological and transcriptomic analyses were conducted to assess the CARASIL phenotype.

Results

At 12 months, histopathological analyses revealed marked thickening of the cerebral

SUBMITTER: Monte B 

PROVIDER: S-EPMC12546807 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature