A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies.pdf (671.41 kB)
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A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies.

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posted on 26.04.2018, 09:11 by G. Banks, G. Lassi, A. Hoerder-Suabedissen, 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, Robert A. Hirst, V. Tucci, P. M. Nolan
Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms. Here we identify and characterise a mouse line carrying a loss of function allele in Katnal1. We show that mutants express behavioural deficits including in circadian rhythms, sleep, anxiety and learning/memory. Furthermore, in the brains of Katnal1 mutant mice we reveal numerous morphological abnormalities and defects in neuronal migration and morphology. Furthermore we demonstrate defects in the motile cilia of the ventricular ependymal cells of mutants, suggesting a role for Katnal1 in the development of ciliary function. We believe the data we present here are the first to associate KATNAL1 with such phenotypes, demonstrating that the protein plays keys roles in a number of processes integral to the development of neuronal function and behaviour.

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Citation

Molecular Psychiatry, 2017, 23, pp. 713-722

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and Inflammation

Version

VoR (Version of Record)

Published in

Molecular Psychiatry

Publisher

Nature Publishing Group

issn

1359-4184

eissn

1476-5578

Acceptance date

10/02/2017

Copyright date

2017

Available date

26/04/2018

Publisher version

https://www.nature.com/articles/mp201754

Language

en

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