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Stochastic Model of Tsc1 Lesions in Mouse Brain

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder due to mutations in either TSC1 or TSC2 that affects many organs with hamartomas and tumors. TSC-associated brain lesions include subependymal nodules, subependymal giant cell astrocytomas and tubers. Neurologic manifestations in TSC...

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Autores principales: Prabhakar, Shilpa, Goto, June, Zuang, Xuan, Sena-Esteves, Miguel, Bronson, Roderick, Brockmann, Jillian, Gianni, Davide, Wojtkiewicz, Gregory R., Chen, John W., Stemmer-Rachamimov, Anat, Kwiatkowski, David J., Breakefield, Xandra O.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655945/
https://www.ncbi.nlm.nih.gov/pubmed/23696872
http://dx.doi.org/10.1371/journal.pone.0064224
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author Prabhakar, Shilpa
Goto, June
Zuang, Xuan
Sena-Esteves, Miguel
Bronson, Roderick
Brockmann, Jillian
Gianni, Davide
Wojtkiewicz, Gregory R.
Chen, John W.
Stemmer-Rachamimov, Anat
Kwiatkowski, David J.
Breakefield, Xandra O.
author_facet Prabhakar, Shilpa
Goto, June
Zuang, Xuan
Sena-Esteves, Miguel
Bronson, Roderick
Brockmann, Jillian
Gianni, Davide
Wojtkiewicz, Gregory R.
Chen, John W.
Stemmer-Rachamimov, Anat
Kwiatkowski, David J.
Breakefield, Xandra O.
author_sort Prabhakar, Shilpa
collection PubMed
description Tuberous sclerosis complex (TSC) is an autosomal dominant disorder due to mutations in either TSC1 or TSC2 that affects many organs with hamartomas and tumors. TSC-associated brain lesions include subependymal nodules, subependymal giant cell astrocytomas and tubers. Neurologic manifestations in TSC comprise a high frequency of mental retardation and developmental disorders including autism, as well as epilepsy. Here, we describe a new mouse model of TSC brain lesions in which complete loss of Tsc1 is achieved in multiple brain cell types in a stochastic pattern. Injection of an adeno-associated virus vector encoding Cre recombinase into the cerebral ventricles of mice homozygous for a Tsc1 conditional allele on the day of birth led to reduced survival, and pathologic findings of enlarged neurons, cortical heterotopias, subependymal nodules, and hydrocephalus. The severity of clinical and pathologic findings as well as survival was shown to be dependent upon the dose and serotype of Cre virus injected. Although several other models of TSC brain disease exist, this model is unique in that the pathology reflects a variety of TSC-associated lesions involving different numbers and types of cells. This model provides a valuable and unique addition for therapeutic assessment.
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spelling pubmed-36559452013-05-21 Stochastic Model of Tsc1 Lesions in Mouse Brain Prabhakar, Shilpa Goto, June Zuang, Xuan Sena-Esteves, Miguel Bronson, Roderick Brockmann, Jillian Gianni, Davide Wojtkiewicz, Gregory R. Chen, John W. Stemmer-Rachamimov, Anat Kwiatkowski, David J. Breakefield, Xandra O. PLoS One Research Article Tuberous sclerosis complex (TSC) is an autosomal dominant disorder due to mutations in either TSC1 or TSC2 that affects many organs with hamartomas and tumors. TSC-associated brain lesions include subependymal nodules, subependymal giant cell astrocytomas and tubers. Neurologic manifestations in TSC comprise a high frequency of mental retardation and developmental disorders including autism, as well as epilepsy. Here, we describe a new mouse model of TSC brain lesions in which complete loss of Tsc1 is achieved in multiple brain cell types in a stochastic pattern. Injection of an adeno-associated virus vector encoding Cre recombinase into the cerebral ventricles of mice homozygous for a Tsc1 conditional allele on the day of birth led to reduced survival, and pathologic findings of enlarged neurons, cortical heterotopias, subependymal nodules, and hydrocephalus. The severity of clinical and pathologic findings as well as survival was shown to be dependent upon the dose and serotype of Cre virus injected. Although several other models of TSC brain disease exist, this model is unique in that the pathology reflects a variety of TSC-associated lesions involving different numbers and types of cells. This model provides a valuable and unique addition for therapeutic assessment. Public Library of Science 2013-05-16 /pmc/articles/PMC3655945/ /pubmed/23696872 http://dx.doi.org/10.1371/journal.pone.0064224 Text en © 2013 Prabhakar et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Prabhakar, Shilpa
Goto, June
Zuang, Xuan
Sena-Esteves, Miguel
Bronson, Roderick
Brockmann, Jillian
Gianni, Davide
Wojtkiewicz, Gregory R.
Chen, John W.
Stemmer-Rachamimov, Anat
Kwiatkowski, David J.
Breakefield, Xandra O.
Stochastic Model of Tsc1 Lesions in Mouse Brain
title Stochastic Model of Tsc1 Lesions in Mouse Brain
title_full Stochastic Model of Tsc1 Lesions in Mouse Brain
title_fullStr Stochastic Model of Tsc1 Lesions in Mouse Brain
title_full_unstemmed Stochastic Model of Tsc1 Lesions in Mouse Brain
title_short Stochastic Model of Tsc1 Lesions in Mouse Brain
title_sort stochastic model of tsc1 lesions in mouse brain
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655945/
https://www.ncbi.nlm.nih.gov/pubmed/23696872
http://dx.doi.org/10.1371/journal.pone.0064224
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