Brain specific knockin of the pathogenic Tubb5 E401K allele causes defects in motor coordination and prepulse inhibition

M. Breuss, A.H. Hansen, L. Landler, D. Keays, Behavioural Brain Research 323 (2017) 47–55.

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Journal Article | Published | English
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Abstract
The generation, migration, and differentiation of neurons requires the functional integrity of the microtubule cytoskeleton. Mutations in the tubulin gene family are known to cause various neurological diseases including lissencephaly, ocular motor disorders, polymicrogyria and amyotrophic lateral sclerosis. We have previously reported that mutations in TUBB5 cause microcephaly that is accompanied by severe intellectual impairment and motor delay. Here we present the characterization of a Tubb5 mouse model that allows for the conditional expression of the pathogenic E401K mutation. Homozygous knockin animals exhibit a severe reduction in brain size and in body weight. These animals do not show any significant impairment in general activity, anxiety, or in the acoustic startle response, however, present with notable defects in motor coordination. When assessed on the static rod apparatus mice took longer to orient and often lost their balance completely. Interestingly, mutant animals also showed defects in prepulse inhibition, a phenotype associated with sensorimotor gating and considered an endophenotype for schizophrenia. This study provides insight into the behavioral consequences of tubulin gene mutations.
Publishing Year
Date Published
2017-04-14
Journal Title
Behavioural Brain Research
Acknowledgement
Austrian Science Fund (FWF) for funding this research [I914,P21092]
Volume
323
Page
47 - 55
ISSN
IST-REx-ID

Cite this

Breuss M, Hansen AH, Landler L, Keays D. Brain specific knockin of the pathogenic Tubb5 E401K allele causes defects in motor coordination and prepulse inhibition. Behavioural Brain Research. 2017;323:47-55. doi:10.1016/j.bbr.2017.01.029
Breuss, M., Hansen, A. H., Landler, L., & Keays, D. (2017). Brain specific knockin of the pathogenic Tubb5 E401K allele causes defects in motor coordination and prepulse inhibition. Behavioural Brain Research, 323, 47–55. https://doi.org/10.1016/j.bbr.2017.01.029
Breuss, Martin, Andi H Hansen, Lukas Landler, and David Keays. “Brain Specific Knockin of the Pathogenic Tubb5 E401K Allele Causes Defects in Motor Coordination and Prepulse Inhibition.” Behavioural Brain Research 323 (2017): 47–55. https://doi.org/10.1016/j.bbr.2017.01.029.
M. Breuss, A. H. Hansen, L. Landler, and D. Keays, “Brain specific knockin of the pathogenic Tubb5 E401K allele causes defects in motor coordination and prepulse inhibition,” Behavioural Brain Research, vol. 323, pp. 47–55, 2017.
Breuss M, Hansen AH, Landler L, Keays D. 2017. Brain specific knockin of the pathogenic Tubb5 E401K allele causes defects in motor coordination and prepulse inhibition. Behavioural Brain Research. 323, 47–55.
Breuss, Martin, et al. “Brain Specific Knockin of the Pathogenic Tubb5 E401K Allele Causes Defects in Motor Coordination and Prepulse Inhibition.” Behavioural Brain Research, vol. 323, Elsevier, 2017, pp. 47–55, doi:10.1016/j.bbr.2017.01.029.
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