TUBB4A mutations result in both glial and neuronal degeneration in an H-ABC leukodystrophy mouse model.

ABSTRACT: Mutations in TUBB4A result in a spectrum of leukodystrophy including Hypomyelination with Atrophy of Basal Ganglia and Cerebellum (H-ABC), a rare hypomyelinating leukodystrophy, often associated with a recurring variant p.Asp249Asn (D249N). We have developed a novel knock-in mouse model harboring heterozygous (Tubb4a^D249N/+) and the homozygous (Tubb4a^D249N/D249N) mutation that recapitulate the progressive motor dysfunction with tremor, dystonia and ataxia seen in H-ABC. Tubb4a^D249N/D249N mice have myelination deficits along with dramatic decrease in mature oligodendrocytes and their progenitor cells. Additionally, a significant loss occurs in the cerebellar granular neurons and striatal neurons in Tubb4a^D249N/D249N<

SUBMITTER: Sase S 

PROVIDER: S-EPMC7255805 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature