Modelling C9orf72 dipeptide repeat proteins of a physiologically relevant size.
Hum Mol Genet
; 25(23): 5069-5082, 2016 12 01.
Article
en En
| MEDLINE
| ID: mdl-27798094
ABSTRACT
C9orf72 expansions are the most common genetic cause of FTLD and MND identified to date. Although being intronic, the expansion is translated into five different dipeptide repeat proteins (DPRs) that accumulate within patients' neurons. Attempts have been made to model DPRs in cell and animals. However, the majority of these use DPRs repeat numbers much shorter than those observed in patients. To address this we have generated a selection of DPR expression constructs with repeat numbers in excess of 1000 repeats, matching what is seen in patients. Small and larger DPRs produce inclusions with similar morphology but different cellular effects. We demonstrate a length dependent effect using electrophysiology with a phenotype only occurring with the longest DPRs. These data highlight the importance of using physiologically relevant repeat numbers when modelling DPRs.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas
/
Dipéptidos
/
Degeneración Lobar Frontotemporal
/
Esclerosis Amiotrófica Lateral
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Hum Mol Genet
Asunto de la revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Reino Unido