An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease.
Autosomal recessive retinal degenerative diseases cause visual impairment and blindness in both humans and dogs. Currently, no standard treatment is available, but pioneering gene therapy-based canine models have been instrumental for clinical trials in humans. To study a novel form of retinal degen...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-03-01
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| Series: | PLoS Genetics |
| Online Access: | http://europepmc.org/articles/PMC6424408?pdf=render |
| _version_ | 1819206997147385856 |
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| author | Suvi Mäkeläinen Marta Gòdia Minas Hellsand Agnese Viluma Daniela Hahn Karim Makdoumi Caroline J Zeiss Cathryn Mellersh Sally L Ricketts Kristina Narfström Finn Hallböök Björn Ekesten Göran Andersson Tomas F Bergström |
| author_facet | Suvi Mäkeläinen Marta Gòdia Minas Hellsand Agnese Viluma Daniela Hahn Karim Makdoumi Caroline J Zeiss Cathryn Mellersh Sally L Ricketts Kristina Narfström Finn Hallböök Björn Ekesten Göran Andersson Tomas F Bergström |
| author_sort | Suvi Mäkeläinen |
| collection | DOAJ |
| description | Autosomal recessive retinal degenerative diseases cause visual impairment and blindness in both humans and dogs. Currently, no standard treatment is available, but pioneering gene therapy-based canine models have been instrumental for clinical trials in humans. To study a novel form of retinal degeneration in Labrador retriever dogs with clinical signs indicating cone and rod degeneration, we used whole-genome sequencing of an affected sib-pair and their unaffected parents. A frameshift insertion in the ATP binding cassette subfamily A member 4 (ABCA4) gene (c.4176insC), leading to a premature stop codon in exon 28 (p.F1393Lfs*1395), was identified. In contrast to unaffected dogs, no full-length ABCA4 protein was detected in the retina of an affected dog. The ABCA4 gene encodes a membrane transporter protein localized in the outer segments of rod and cone photoreceptors. In humans, the ABCA4 gene is associated with Stargardt disease (STGD), an autosomal recessive retinal degeneration leading to central visual impairment. A hallmark of STGD is the accumulation of lipofuscin deposits in the retinal pigment epithelium (RPE). The discovery of a canine homozygous ABCA4 loss-of-function mutation may advance the development of dog as a large animal model for human STGD. |
| first_indexed | 2024-12-23T05:16:29Z |
| format | Article |
| id | doaj.art-440e2dd2ef7541c0a70a7c12f3d6f9ec |
| institution | Directory Open Access Journal |
| issn | 1553-7390 1553-7404 |
| language | English |
| last_indexed | 2024-12-23T05:16:29Z |
| publishDate | 2019-03-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Genetics |
| spelling | doaj.art-440e2dd2ef7541c0a70a7c12f3d6f9ec2022-12-21T17:58:49ZengPublic Library of Science (PLoS)PLoS Genetics1553-73901553-74042019-03-01153e100787310.1371/journal.pgen.1007873An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease.Suvi MäkeläinenMarta GòdiaMinas HellsandAgnese VilumaDaniela HahnKarim MakdoumiCaroline J ZeissCathryn MellershSally L RickettsKristina NarfströmFinn HallböökBjörn EkestenGöran AnderssonTomas F BergströmAutosomal recessive retinal degenerative diseases cause visual impairment and blindness in both humans and dogs. Currently, no standard treatment is available, but pioneering gene therapy-based canine models have been instrumental for clinical trials in humans. To study a novel form of retinal degeneration in Labrador retriever dogs with clinical signs indicating cone and rod degeneration, we used whole-genome sequencing of an affected sib-pair and their unaffected parents. A frameshift insertion in the ATP binding cassette subfamily A member 4 (ABCA4) gene (c.4176insC), leading to a premature stop codon in exon 28 (p.F1393Lfs*1395), was identified. In contrast to unaffected dogs, no full-length ABCA4 protein was detected in the retina of an affected dog. The ABCA4 gene encodes a membrane transporter protein localized in the outer segments of rod and cone photoreceptors. In humans, the ABCA4 gene is associated with Stargardt disease (STGD), an autosomal recessive retinal degeneration leading to central visual impairment. A hallmark of STGD is the accumulation of lipofuscin deposits in the retinal pigment epithelium (RPE). The discovery of a canine homozygous ABCA4 loss-of-function mutation may advance the development of dog as a large animal model for human STGD.http://europepmc.org/articles/PMC6424408?pdf=render |
| spellingShingle | Suvi Mäkeläinen Marta Gòdia Minas Hellsand Agnese Viluma Daniela Hahn Karim Makdoumi Caroline J Zeiss Cathryn Mellersh Sally L Ricketts Kristina Narfström Finn Hallböök Björn Ekesten Göran Andersson Tomas F Bergström An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease. PLoS Genetics |
| title | An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease. |
| title_full | An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease. |
| title_fullStr | An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease. |
| title_full_unstemmed | An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease. |
| title_short | An ABCA4 loss-of-function mutation causes a canine form of Stargardt disease. |
| title_sort | abca4 loss of function mutation causes a canine form of stargardt disease |
| url | http://europepmc.org/articles/PMC6424408?pdf=render |
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