Elevated body temperature exacerbates arrhythmia and seizure-like activity in a zebrafish model of Timothy syndrome.

ABSTRACT: Timothy syndrome (TS) is a multisystem disorder with autistic-like features, seizures and arrhythmia as the main symptoms. Most TS cases are caused by a de novo single amino acid substitution G406R in the CACNA1C gene that encodes the pore-forming subunit of the voltage-gated L-type calcium channel Ca_V1.2. We generated a zebrafish model of TS with a homologous amino acid substitution in the cacna1c-encoded protein. Unlike patients, heterozygous mutants showed only mild impairments with no changes in mortality. However, homozygous mutants showed increased mortality, arrhythmias, neural activity and sensitivity to pentylenetetrazole-induced seizure-like behavior. Mutants also exhibited microcephaly, cerebellar hypotrophy and abnormal development of GABAergic n

SUBMITTER: Semenova SA 

PROVIDER: S-EPMC12190319 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature