A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice
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Le résumé fourni par la source
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease. Loss of the survival motor neuron (SMN1) gene, in the presence of the SMN2 gene causes SMA. SMN functions in snRNP assembly in all cell types, however, it is unclear how this function results in specifically motor neuron cell death. Lack of endogenous mouse SMN (Smn) in mice results in embryonic lethality. Introduction of two copies of human SMN2 results in a mouse with severe SMA, while one copy of SMN2 is insufficient to overcome embryonic lethality. We show that SMN(A111G), an allele capable of snRNP assembly, can rescue mice that lack Smn and contain either one or two copies of SMN2 (SMA mice). The correction of SMA in these animals was directly correlated with snRNP assembly activity in spinal cord, as was correction of snRNA levels. These data support snRNP assembly as being the critical function affected in SMA and suggests that the levels of snRNPs are critical to motor neurons. Furthermore, SMN(A111G) cannot rescue Smn-/- mice without SMN2 suggesting that both SMN(A111G) and SMN from SMN2 undergo intragenic complementation in vivo to function in heteromeric complexes that have greater function than either allele alone. The oligomer composed of limiting full-length SMN and SMN(A111G) has substantial snRNP assembly activity. Also, the SMN(A2G) and SMN(A111G) alleles in vivo did not complement each other leading to the possibility that these mutations could affect the same function.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- A SMN missense mutation complements SMN2 restoring snRNPs and rescuing SMA mice
- Date Crossref
- 27/03/2009
- Éditeur
- Oxford University Press (OUP)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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The Ohio State University Department of Molecular and Cellular Biochemistry pays non établi dans la noticeUniversité ou école supérieure
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Columbia University Irving Medical Center pays non établi dans la noticeÉtablissement de santé
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Johns Hopkins Hospital Department of Pediatrics pays non établi dans la noticeÉtablissement de santé
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Jackson Laboratory pays non établi dans la noticeOrganisation à but non lucratif
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Department of Molecular and Cellular Biochemistry pays non établi dans la noticeInstitution
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Columbia University Medical Center Department of Pathology and Cell Biology pays non établi dans la noticeUniversité ou école supérieure
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Department of Neurology pays non établi dans la noticeInstitution
Department of Molecular and Cellular Biochemistry — The Ohio State University, Columbia University Irving Medical Center et Department of Pediatrics — Johns Hopkins Hospital, avec 4 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.