A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies

• DOI: 10.1038/mp.2017.54
• Publication Date: 2017-04-04T09:45:42Z
• Authors: G Banks; G Lassi; A Hoerder-Suabedi...; F Tinarelli; M M Simon; A Wilcox; P Lau; T N Lawson; S Johnson; A Rutman; M Sweeting; J E Chesham; A R Barnard; N Horner; H Westerberg; L B Smith; Z Molnár; M H Hastings; R A Hirst; V Tucci; P M Nolan
• Keywords: Loss function; Microcephaly

Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule is fundamental to many dynamic neural processes, little known regarding the role family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating KATNAL1 locus humans result intellectual disability microcephaly suggest may play prominent CNS; however, such associations lack functional data required highlight potential mechanisms which link gene disease symptoms. Here we identify characterise mouse line carrying loss function allele Katnal1. We show mutants express behavioural deficits including circadian rhythms, sleep, anxiety learning/memory. Furthermore, brains Katnal1 mutant mice reveal numerous morphological abnormalities defects neuronal migration morphology. Furthermore demonstrate motile cilia ventricular ependymal cells mutants, suggesting for ciliary believe present here are first associate with phenotypes, demonstrating protein plays keys roles number processes integral behaviour.