Postnatal and adult consequences of loss of huntingtin during development: Implications for Huntington's disease.
Neurobiol Dis
; 96: 144-155, 2016 Dec.
Article
en En
| MEDLINE
| ID: mdl-27623015
The mutation in huntingtin (mHtt) leads to a spectrum of impairments in the developing forebrain of Huntington's disease (HD) mouse models. Whether these developmental alterations are due to loss- or gain-of-function mechanisms and contribute to HD pathogenesis is unknown. We examined the role of selective loss of huntingtin (Htt) function during development on postnatal vulnerability to cell death. We employed mice expressing very low levels of Htt throughout embryonic life to postnatal day 21 (Hdhdâ¢hyp). We demonstrated that Hdhdâ¢hyp mice exhibit: (1) late-life striatal and cortical neuronal degeneration; (2) neurological and skeletal muscle alterations; and (3) white matter tract impairments and axonal degeneration. Hdhdâ¢hyp embryos also exhibited subpallial heterotopias, aberrant striatal maturation and deregulation of gliogenesis. These results indicate that developmental deficits associated with Htt functions render cells present at discrete neural foci increasingly susceptible to cell death, thus implying the potential existence of a loss-of-function developmental component to HD pathogenesis.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Discapacidades del Desarrollo
/
Enfermedad de Huntington
/
Enfermedades Neurodegenerativas
/
Proteína Huntingtina
/
Mutación
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Neurobiol Dis
Asunto de la revista:
NEUROLOGIA
Año:
2016
Tipo del documento:
Article
Pais de publicación:
Estados Unidos