Further molecular characterisation of the OVT73 transgenic sheep model of Huntington's disease identifies cortical aggregates.
J Huntingtons Dis
; 2(3): 279-95, 2013.
Article
en En
| MEDLINE
| ID: mdl-25062676
ABSTRACT
BACKGROUND:
Huntington's disease is a neurodegenerative disorder, typically with clinical manifestations in adult years, caused by an expanded polyglutamine-coding repeat in HTT. There are no treatments that delay or prevent the onset or progression of this devastating disease. OBJECTIVE ANDMETHODS:
In order to study its pre-symptomatic molecular progression and provide a large mammalian model for determining natural history of the disease and for therapeutic testing, we generated and previously reported on lines of transgenic sheep carrying a full length human HTT cDNA transgene, with expression driven by a minimal HTT promoter. We report here further characterization of our preferred line, OVT73.RESULTS:
This line reliably expresses the expanded human huntingtin protein at modest, but readily detectable levels throughout the brain, including the striatum and cortex. Transmission of the 73 unit glutamine coding repeat was relatively stable over three generations. At the first time-point of a longitudinal study, animals sacrificed at 6 months (7 transgenic, 7 control) showed reduced striatum GABAA α1 receptor, and globus pallidus leu-enkephalin immunoreactivity. Two of three 18 month old animals sacrificed revealed cortical neuropil aggregates. Furthermore, neuronal intranuclear inclusions were identified in the piriform cortex of a single 36 month old animal in addition to cortical neuropil aggregates.CONCLUSIONS:
Taken together, these data indicate that the OVT73 transgenic sheep line will progressively reveal early HD pathology and allow therapeutic testing over a period of time relevant to human patients.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Animales Modificados Genéticamente
/
Corteza Cerebral
/
Enfermedad de Huntington
/
Oveja Doméstica
/
Modelos Animales de Enfermedad
Tipo de estudio:
Observational_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
J Huntingtons Dis
Año:
2013
Tipo del documento:
Article
País de afiliación:
Nueva Zelanda