RGD Reference Report - AAV-mediated tyrosinase gene transfer restores melanogenesis and retinal function in a model of oculo-cutaneous albinism type I (OCA1). - Rat Genome Database

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AAV-mediated tyrosinase gene transfer restores melanogenesis and retinal function in a model of oculo-cutaneous albinism type I (OCA1).

Authors: Gargiulo, A  Bonetti, C  Montefusco, S  Neglia, S  Di Vicino, U  Marrocco, E  Corte, MD  Domenici, L  Auricchio, A  Surace, EM 
Citation: Gargiulo A, etal., Mol Ther. 2009 Aug;17(8):1347-54. doi: 10.1038/mt.2009.112. Epub 2009 May 12.
RGD ID: 8694335
Pubmed: PMID:19436266   (View Abstract at PubMed)
PMCID: PMC2835246   (View Article at PubMed Central)
DOI: DOI:10.1038/mt.2009.112   (Journal Full-text)

Oculo-cutaneous albinism type 1 (OCA1) is characterized by congenital hypopigmentation and is due to mutations in the TYROSINASE gene (TYR). In this study, we have characterized the morpho-functional consequences of the lack of tyrosinase activity in the spontaneous null mouse model of OCA1 (Tyr(c-2j)). Here, we show that adult Tyr(c-2j) mice have several retinal functional anomalies associated with photoreceptor loss. To test whether these anomalies are reversible upon TYR complementation, we performed intraocular administration of an adeno-associated virus (AAV)-based vector, encoding the human TYR gene, in adult Tyr(c-2j) mice. This resulted in melanosome biogenesis and ex novo synthesis of melanin in both neuroectodermally derived retinal pigment epithelium (RPE) and in neural crest-derived choroid and iris melanocytes. Ocular melanin accumulation prevented progressive photoreceptor degeneration and resulted in restoration of retinal function. Our results reveal novel properties of pigment cells and show that the developmental anomalies of albino mice are associated with defects occurring in postnatal life, adding novel insights on OCA1 disease pathogenesis. In addition, we provide proof-of-principle of an effective gene-based strategy relevant for future application in albino patients.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Objects Annotated

Genes (Rattus norvegicus)
Tyr  (tyrosinase)

Genes (Mus musculus)
Tyr  (tyrosinase)

Genes (Homo sapiens)
TYR  (tyrosinase)


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