Dataset Information

AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisis.

ABSTRACT: Degeneration of photoreceptors is a common feature of ciliopathies, owing to the importance of the specialized ciliary structure of these cells. Mutations in AHI1, which encodes a cilium-localized protein, have been shown to cause a form of Joubert syndrome that is highly penetrant for retinal degeneration. We show that Ahi1-null mice fail to form retinal outer segments and have abnormal distribution of opsin throughout their photoreceptors. Apoptotic cell death of photoreceptors occurs rapidly between 2 and 4 weeks of age in these mice and is significantly (P = 0.00175 and 0.00613) delayed by a reduced dosage of opsin. This phenotype also shows dosage-sensitive genetic interactions with Nphp1, another ciliopathy-related gene. Although it is not a primary cause of retinal blindness in humans, we show that an allele of AHI1 is associated with a more than sevenfold increase in relative risk of retinal degeneration within a cohort of individuals with the hereditary kidney disease nephronophthisis. Our data support context-specific roles for AHI1 as a contributor to retinopathy and show that AHI1 may explain a proportion of the variability in retinal phenotypes observed in nephronophthisis.

SUBMITTER: Louie CM

PROVIDER: S-EPMC2884967 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisis.

Louie Carrie M CM Caridi Gianluca G Lopes Vanda S VS Brancati Francesco F Kispert Andreas A Lancaster Madeline A MA Schlossman Andrew M AM Otto Edgar A EA Leitges Michael M Gröne Hermann-Josef HJ Lopez Irma I Gudiseva Harini V HV O'Toole John F JF Vallespin Elena E Ayyagari Radha R Ayuso Carmen C Cremers Frans P M FP den Hollander Anneke I AI Koenekoop Robert K RK Dallapiccola Bruno B Ghiggeri Gian Marco GM Hildebrandt Friedhelm F Valente Enza Maria EM Williams David S DS Gleeson Joseph G JG

Nature genetics 20100117 2

Degeneration of photoreceptors is a common feature of ciliopathies, owing to the importance of the specialized ciliary structure of these cells. Mutations in AHI1, which encodes a cilium-localized protein, have been shown to cause a form of Joubert syndrome that is highly penetrant for retinal degeneration. We show that Ahi1-null mice fail to form retinal outer segments and have abnormal distribution of opsin throughout their photoreceptors. Apoptotic cell death of photoreceptors occurs rapidly ...[more]

PMID: 20081859

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Dataset Information

AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisis.

Publications

AHI1 is required for photoreceptor outer segment development and is a modifier for retinal degeneration in nephronophthisis.

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