دورية أكاديمية
أعرض في EDS

A Retroviral CRISPR-Cas9 System for Cellular Autism-Associated Phenotype Discovery in Developing Neurons.

التفاصيل البيبلوغرافية
العنوان: A Retroviral CRISPR-Cas9 System for Cellular Autism-Associated Phenotype Discovery in Developing Neurons.
المؤلفون: Williams MR; Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA., Fricano-Kugler CJ; Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA., Getz SA; Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA., Skelton PD; Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA., Lee J; Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA., Rizzuto CP; Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA., Geller JS; Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA., Li M; Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA., Luikart BW; Department of Physiology and Neurobiology, Geisel School of Medicine at Dartmouth College, USA.
المصدر: Scientific reports [Sci Rep] 2016 May 10; Vol. 6, pp. 25611. Date of Electronic Publication: 2016 May 10.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH: CRISPR-Cas Systems*, Autistic Disorder/*genetics , Neurons/*metabolism , Retroviridae/*genetics, Animals ; Autistic Disorder/pathology ; Cell Enlargement ; Female ; Gene Editing/methods ; Humans ; Katanin/genetics ; Male ; Mice, Inbred C57BL ; Mutation ; Neurons/pathology ; PTEN Phosphohydrolase/genetics ; Phenotype ; RNA Interference
مستخلص: Retroviruses expressing a fluorescent protein, Cas9, and a small guide RNA are used to mimic nonsense PTEN mutations from autism patients in developing mouse neurons. We compare the cellular phenotype elicited by CRISPR-Cas9 to those elicited using shRNA or Cre/Lox technologies and find that knockdown or knockout (KO) produced a corresponding moderate or severe neuronal hypertrophy in all cells. In contrast, the Cas9 approach produced missense and nonsense Pten mutations, resulting in a mix of KO-equivalent hypertrophic and wild type-like phenotypes. Importantly, despite this mixed phenotype, the neuronal hypertrophy resulting from Pten loss was evident on average in the population of manipulated cells. Having reproduced the known Pten KO phenotype using the CRISPR-Cas9 system we design viruses to target a gene that has recently been associated with autism, KATNAL2. Katnal2 deletion in the mouse results in decreased dendritic arborization of developing neurons. We conclude that retroviral implementation of the CRISPR-Cas9 system is an efficient system for cellular phenotype discovery in wild-type animals.
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معلومات مُعتمدة: R01 MH097949 United States MH NIMH NIH HHS
المشرفين على المادة: EC 3.1.3.67 (PTEN Phosphohydrolase)
EC 5.6.1.1 (KATNAL2 protein, mouse)
EC 5.6.1.1 (Katanin)
تواريخ الأحداث: Date Created: 20160511 Date Completed: 20180326 Latest Revision: 20191210
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC4861960
DOI: 10.1038/srep25611
PMID: 27161796
قاعدة البيانات: MEDLINE
الوصف
تدمد:2045-2322
DOI:10.1038/srep25611