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The domestic cat as a large animal model for characterization of disease and therapeutic intervention in hereditary retinal blindness.

Narfström K, Holland Deckman K, Menotti-Raymond M - J Ophthalmol (2011)

Bottom Line: Two well-characterized feline models are addressed in this paper.The first model is the autosomal recessive, slowly progressive, late-onset, rod-cone degenerative disease caused by a mutation in the CEP290 gene.The second model addressed in this paper is the autosomal dominant early onset rod cone dysplasia, putatively caused by the mutation found in the CRX gene.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, Mason Eye Institute, University of Missouri-Columbia, MO 65211, USA.

ABSTRACT
Large mammals, including canids and felids, are affected by spontaneously occurring hereditary retinal diseases with similarities to those of humans. The large mammal models may be used for thorough clinical characterization of disease processes, understanding the effects of specific mutations, elucidation of disease mechanisms, and for development of therapeutic intervention. Two well-characterized feline models are addressed in this paper. The first model is the autosomal recessive, slowly progressive, late-onset, rod-cone degenerative disease caused by a mutation in the CEP290 gene. The second model addressed in this paper is the autosomal dominant early onset rod cone dysplasia, putatively caused by the mutation found in the CRX gene. Therapeutic trials have been performed mainly in the former type including stem cell therapy, retinal transplantation, and development of ocular prosthetics. Domestic cats, having large human-like eyes with comparable spontaneous retinal diseases, are also considered useful for gene replacement therapy, thus functioning as effective model systems for further research.

No MeSH data available.


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CRX protein structure in Felis catus. Wildtype feline CRX protein (a) compared to the putative truncated CRX protein (b).  The exon splice junctions are noted as “Y”.  The start codon and stop codons are labeled as (*) and (X), respectively. The protein domains are highlighted as shaded boxes and defined as the homeobox, the WSP domain, the transcriptional transactivation domains 1 and 2 (TTD1 and TTD2), and the OTX tail.  Domains are drawn to scale. Reproduced with permission from [26].
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fig4: CRX protein structure in Felis catus. Wildtype feline CRX protein (a) compared to the putative truncated CRX protein (b). The exon splice junctions are noted as “Y”. The start codon and stop codons are labeled as (*) and (X), respectively. The protein domains are highlighted as shaded boxes and defined as the homeobox, the WSP domain, the transcriptional transactivation domains 1 and 2 (TTD1 and TTD2), and the OTX tail. Domains are drawn to scale. Reproduced with permission from [26].

Mentions: The molecular genetic basis for Rdy was recently elucidated [26]. A single-base deletion in the CRX gene introduces a frameshift and a stop codon immediately downstream, truncating a region previously demonstrated as critical for gene function [26, 54] (Figure 4). The CRX gene product is critical in transcriptional activation of a number of genes involved in photoreceptor development and maintenance [55, 56]. In humans, mutations in CRX are associated with human AD cone-rod dystrophy (CoRD), and both AD and AR Leber's congenital amaurosis (LCA) [54, 57–59]. The Rdy cat is the first large animal model for CRX-linked spontaneous retinal disease. A large screening of cat breeds has failed to detect any other domestic feline breeds with the disease allele [26].


The domestic cat as a large animal model for characterization of disease and therapeutic intervention in hereditary retinal blindness.

Narfström K, Holland Deckman K, Menotti-Raymond M - J Ophthalmol (2011)

CRX protein structure in Felis catus. Wildtype feline CRX protein (a) compared to the putative truncated CRX protein (b).  The exon splice junctions are noted as “Y”.  The start codon and stop codons are labeled as (*) and (X), respectively. The protein domains are highlighted as shaded boxes and defined as the homeobox, the WSP domain, the transcriptional transactivation domains 1 and 2 (TTD1 and TTD2), and the OTX tail.  Domains are drawn to scale. Reproduced with permission from [26].
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3090773&req=5

fig4: CRX protein structure in Felis catus. Wildtype feline CRX protein (a) compared to the putative truncated CRX protein (b). The exon splice junctions are noted as “Y”. The start codon and stop codons are labeled as (*) and (X), respectively. The protein domains are highlighted as shaded boxes and defined as the homeobox, the WSP domain, the transcriptional transactivation domains 1 and 2 (TTD1 and TTD2), and the OTX tail. Domains are drawn to scale. Reproduced with permission from [26].
Mentions: The molecular genetic basis for Rdy was recently elucidated [26]. A single-base deletion in the CRX gene introduces a frameshift and a stop codon immediately downstream, truncating a region previously demonstrated as critical for gene function [26, 54] (Figure 4). The CRX gene product is critical in transcriptional activation of a number of genes involved in photoreceptor development and maintenance [55, 56]. In humans, mutations in CRX are associated with human AD cone-rod dystrophy (CoRD), and both AD and AR Leber's congenital amaurosis (LCA) [54, 57–59]. The Rdy cat is the first large animal model for CRX-linked spontaneous retinal disease. A large screening of cat breeds has failed to detect any other domestic feline breeds with the disease allele [26].

Bottom Line: Two well-characterized feline models are addressed in this paper.The first model is the autosomal recessive, slowly progressive, late-onset, rod-cone degenerative disease caused by a mutation in the CEP290 gene.The second model addressed in this paper is the autosomal dominant early onset rod cone dysplasia, putatively caused by the mutation found in the CRX gene.

View Article: PubMed Central - PubMed

Affiliation: Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, Mason Eye Institute, University of Missouri-Columbia, MO 65211, USA.

ABSTRACT
Large mammals, including canids and felids, are affected by spontaneously occurring hereditary retinal diseases with similarities to those of humans. The large mammal models may be used for thorough clinical characterization of disease processes, understanding the effects of specific mutations, elucidation of disease mechanisms, and for development of therapeutic intervention. Two well-characterized feline models are addressed in this paper. The first model is the autosomal recessive, slowly progressive, late-onset, rod-cone degenerative disease caused by a mutation in the CEP290 gene. The second model addressed in this paper is the autosomal dominant early onset rod cone dysplasia, putatively caused by the mutation found in the CRX gene. Therapeutic trials have been performed mainly in the former type including stem cell therapy, retinal transplantation, and development of ocular prosthetics. Domestic cats, having large human-like eyes with comparable spontaneous retinal diseases, are also considered useful for gene replacement therapy, thus functioning as effective model systems for further research.

No MeSH data available.


Related in: MedlinePlus