Mutations in α-Tubulin and Their Effects on Neuronal Migration
Author Information
Author(s): Keays David A., Tian Guoling, Poirier Karine, Huang Guo-Jen, Siebold Christian, Cleak James, Oliver Peter L., Fray Martin, Harvey Robert J., Molnár Zoltán, Piñon Maria C., Dear Neil, Valdar William, Brown Steve D.M., Davies Kay E., Rawlins J. Nicholas P., Cowan Nicholas J., Nolan Patrick, Chelly Jamel, Flint Jonathan
Primary Institution: Wellcome Trust Centre for Human Genetics, University of Oxford
Hypothesis
The S140G mutation in α-1 tubulin affects GTP binding and leads to impaired neuronal migration.
Conclusion
Mutations in the human homolog of α-1 tubulin, TUBA3, are linked to lissencephaly and other cortical migration disorders.
Supporting Evidence
- Two patients with de novo mutations in TUBA3 were identified, linking the mutation to lissencephaly.
- The S140G mutation in Tuba1 was shown to reduce GTP binding and affect tubulin heterodimer formation.
- Behavioral tests indicated that Jna/+ mice exhibited significant deficits in spatial working memory.
- Histological examination revealed abnormal lamination in the hippocampus of Jna/+ mice.
Takeaway
Some changes in a protein called α-tubulin can make it hard for brain cells to move to the right places, which can cause problems in how the brain is built.
Methodology
The study involved screening a large number of mice for behavioral changes and mapping genetic mutations associated with these changes.
Limitations
The study primarily focused on a specific mutation and its effects, which may not represent all cases of lissencephaly.
Participant Demographics
The study included a cohort of 9216 mice and 40 human patients with developmental brain anomalies.
Statistical Information
P-Value
0.01
Statistical Significance
p<0.0001
Digital Object Identifier (DOI)
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