Cell Type-Specific Contributions to the TSC Neuropathology
Technical Report,01 Aug 2016,31 Jul 2019
Rutgers, the State University of New Jersey Piscataway United States
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Mutations in the human TSC2 gene cause tuberous sclerosis complex TSC, a developmental disorder characterized by tumor susceptibility and neurological manifestations. To better understand the disease, we generated an animal model in which the mouse Tsc2 gene is disrupted exclusively in excitatory neurons of the forebrain. We investigated how heterozygous and homozygous Tsc2 mutations affect the development of mutant excitatory neurons as well as other surrounding brain cells, in vivo and in vitro. We found that heterozygous mutations of Tsc2 in the excitatory neurons of the forebrain have modest effects on their growth, whereas homozygous loss disrupts the maturation not only of excitatory neurons and their synapses, but also disrupts the development of inhibitory neurons and their synapses. These combined effects likely contribute to altered neuronal activity and increased seizure susceptibility in TSC.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology