| First Author | Kang R | Year | 2024 |
| Journal | PLoS Biol | Volume | 22 |
| Issue | 5 | Pages | e3002596 |
| PubMed ID | 38718086 | Mgi Jnum | J:357380 |
| Mgi Id | MGI:7642523 | Doi | 10.1371/journal.pbio.3002596 |
| Citation | Kang R, et al. (2024) Loss of Katnal2 leads to ependymal ciliary hyperfunction and autism-related phenotypes in mice. PLoS Biol 22(5):e3002596 |
| abstractText | Autism spectrum disorders (ASD) frequently accompany macrocephaly, which often involves hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-regulatory protein strongly linked to ASD, but it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule- and ASD-related molecular, synaptic, brain, and behavioral phenotypes. We found that Katnal2-KO mice display ASD-like social communication deficits and age-dependent progressive ventricular enlargements. The latter involves increased length and beating frequency of motile cilia on ependymal cells lining ventricles. Katnal2-KO hippocampal neurons surrounded by enlarged lateral ventricles show progressive synaptic deficits that correlate with ASD-like transcriptomic changes involving synaptic gene down-regulation. Importantly, early postnatal Katnal2 re-expression prevents ciliary, ventricular, and behavioral phenotypes in Katnal2-KO adults, suggesting a causal relationship and a potential treatment. Therefore, Katnal2 negatively regulates ependymal ciliary function and its deletion in mice leads to ependymal ciliary hyperfunction and hydrocephalus accompanying ASD-related behavioral, synaptic, and transcriptomic changes. |
