Intragenic complementation of amino and carboxy terminal SMN missense mutations can rescue Smn null mice.
Hum Mol Genet
; 29(21): 3493-3503, 2020 11 01.
Article
en En
| MEDLINE
| ID: mdl-33084884
ABSTRACT
Spinal muscular atrophy is caused by reduced levels of SMN resulting from the loss of SMN1 and reliance on SMN2 for the production of SMN. Loss of SMN entirely is embryonic lethal in mammals. There are several SMN missense mutations found in humans. These alleles do not show partial function in the absence of wild-type SMN and cannot rescue a null Smn allele in mice. However, these human SMN missense allele transgenes can rescue a null Smn allele when SMN2 is present. We find that the N- and C-terminal regions constitute two independent domains of SMN that can be separated genetically and undergo intragenic complementation. These SMN protein heteromers restore snRNP assembly of Sm proteins onto snRNA and completely rescue both survival of Smn null mice and motor neuron electrophysiology demonstrating that the essential functional unit of SMN is the oligomer.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Atrofia Muscular Espinal
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Proteína 1 para la Supervivencia de la Neurona Motora
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Proteína 2 para la Supervivencia de la Neurona Motora
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Neuronas Motoras
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2020
Tipo del documento:
Article