A heterozygous mutation in tubulin,beta 2B
(
Tubb2b
) causes cognitive deficits and hippocampal disorganization |
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Authors: | Rolf W Stottmann Ashley Driver Arnold Gutierrez Matthew R Skelton Michael Muntifering Christopher Stepien Luke Knudson Matthew Kofron Charles V Vorhees Michael T Williams |
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Institution: | 1. Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA;2. Graduate Program in Neuroscience, University of Cincinnati College of Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA;3. Division of Developmental Biology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA;4. Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA |
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Abstract: | Development of the mammalian forebrain requires a significant contribution from tubulin proteins to physically facilitate both the large number of mitoses in the neurogenic brain (in the form of mitotic spindles) as well as support cellular scaffolds to guide radial migration (radial glial neuroblasts). Recent studies have identified a number of mutations in human tubulin genes affecting the forebrain, including TUBB2B . We previously identified a mouse mutation in Tubb2b and we show here that mice heterozygous for this missense mutation in Tubb2b have significant cognitive defects in spatial learning and memory. We further showed reduced hippocampal long‐term potentiation consistent with these defects. In addition to the behavioural and physiological deficits, we show here abnormal hippocampal morphology. Taken together, these phenotypes suggest that heterozygous mutations in tubulin genes result in cognitive deficits not previously appreciated. This has implications for design and interpretation of genetic testing for humans with intellectual disability disorders. |
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Keywords: |
CA3
CNS
congenital malformation development hippocampus learning mouse neural development tubb2b tubulin |
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