Academic Journal
TUBB4A mutations result in both glial and neuronal degeneration in an H-ABC leukodystrophy mouse model
| Τίτλος: | TUBB4A mutations result in both glial and neuronal degeneration in an H-ABC leukodystrophy mouse model |
|---|---|
| Συγγραφείς: | Sase, Sunetra, Almad, Akshata A, Boecker, C Alexander, Guedes-Dias, Pedro, Li, Jian J, Takanohashi, Asako, Patel, Akshilkumar, McCaffrey, Tara, Patel, Heta, Sirdeshpande, Divya, Curiel, Julian, Shih-Hwa Liu, Judy, Padiath, Quasar, Holzbaur, Erika LF, Scherer, Steven S, Vanderver, Adeline |
| Συνεισφορές: | The Commonwealth Universal Research Enhancement, National Institutes of Health, German Research Foundation |
| Πηγή: | eLife ; volume 9 ; ISSN 2050-084X |
| Στοιχεία εκδότη: | eLife Sciences Publications, Ltd |
| Έτος έκδοσης: | 2020 |
| Συλλογή: | eLife (E-Journal - via CrossRef) |
| Περιγραφή: | Mutations in TUBB4A result in a spectrum of leukodystrophy including Hypomyelination with Atrophy of Basal Ganglia and Cerebellum (H-ABC), a rare hypomyelinating leukodystrophy, often associated with a recurring variant p.Asp249Asn (D249N). We have developed a novel knock-in mouse model harboring heterozygous (Tubb4aD249N/+) and the homozygous (Tubb4aD249N/D249N) mutation that recapitulate the progressive motor dysfunction with tremor, dystonia and ataxia seen in H-ABC. Tubb4aD249N/D249N mice have myelination deficits along with dramatic decrease in mature oligodendrocytes and their progenitor cells. Additionally, a significant loss occurs in the cerebellar granular neurons and striatal neurons in Tubb4aD249N/D249N mice. In vitro studies show decreased survival and dysfunction in microtubule dynamics in neurons from Tubb4aD249N/D249N mice. Thus Tubb4aD249N/D249N mice demonstrate the complex cellular physiology of H-ABC, likely due to independent effects on oligodendrocytes, striatal neurons, and cerebellar granule cells in the context of altered microtubule dynamics, with profound neurodevelopmental deficits. |
| Τύπος εγγράφου: | article in journal/newspaper |
| Γλώσσα: | English |
| DOI: | 10.7554/elife.52986 |
| Διαθεσιμότητα: | https://doi.org/10.7554/elife.52986 https://cdn.elifesciences.org/articles/52986/elife-52986-v1.pdf https://cdn.elifesciences.org/articles/52986/elife-52986-v1.xml https://elifesciences.org/articles/52986 |
| Rights: | http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ ; http://creativecommons.org/licenses/by/4.0/ |
| Αριθμός Καταχώρησης: | edsbas.8C2C5AE7 |
| Βάση Δεδομένων: | BASE |
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