Identification and characterisation of the retinitis pigmentosa 1-like1 gene (RP1L1): a novel candidate for retinal degenerations

Abstract

Retinitis pigmentosa (RP) is the most common form of inherited retinopathy, with an approximate incidence of 1 in 3700 individuals worldwide. Mutations in the retinitis pigmentosa 1 (RP1) gene are responsible for about 5 -10% cases of autosomal dominant RP. The RP1 gene is specifically expressed in the photoreceptor layers of the postnatal retina and encodes a predicted protein characterised by the presence of two doublecortin (DC) domains, known to be implicated in microtubule binding. We identified and characterised, both in human and in mouse, a novel mammalian gene, termed Retinitis Pigmentosa1-like1 (RP1L1), because of its significant sequence similarity to the RP1 gene product. The sequence homology between RP1 and RP1L1 was found to be mostly restricted to the DC domains and to the N-terminal region, including the first 350 amino acids. The RP1L1 gene was also found to be conserved in distant vertebrates, since we identified a homologue in Fugu rubripes (pufferfish). Similar to RP1, RP1L1 expression is restricted to the postnatal retina, as determined by semiquantitative reverse transcriptase-PCR and Northern analysis. The retina-specific expression and the sequence similarity to RP1 render RP1L1 a potential candidate for inherited retinal disorders.

Putative digenic inheritance of heterozygousRP1L1andC2orf71null mutations in syndromic retinal dystrophy

“…RP1L1 is expressed primarily in cones and rods. 17 The first 350 amino acids are conserved and share high similarity with RP1, a protein that can be mutated in autosomal dominant and recessive forms of RP. 18–20 This conserved region contains two doublecortin domains.…”

Clinical Characteristics of Occult Macular Dystrophy in Family With Mutation of Rp1l1 Gene

“…12 The RP1L1 gene was originally cloned as a gene derived from common ancestors as a retinitis pigmentosa 1 (RP1) gene, which is responsible for 5-10% of autosomal dominant retinitis pigmentosa worldwide, on the same Chromosome 8. [13][14][15][16][17] A number of attempts have been made to identify mutations in RP1L1 in various retinitis pigmentosa patients with no success. An immunohistochemical study on cynomolgus monkeys showed that RP1L1 was expressed in rod and cone photoreceptors, and RP1L1 is thought to play important roles in the morphogenesis of the photoreceptors.…”

“…An immunohistochemical study on cynomolgus monkeys showed that RP1L1 was expressed in rod and cone photoreceptors, and RP1L1 is thought to play important roles in the morphogenesis of the photoreceptors. 13,18 Heterozygous RP1L1 knockout mice were reported to be normal, whereas homozygous knockout mice develop subtle retinal degeneration. 18 However, the RP1L1 protein has a very low degree of overall sequence identity (39%) between humans and mice compared with the average values of sequence similarity observed between humans and mice proteins.…”

Use of RNA Interference by In Utero Electroporation to Study Cortical Development: The Example of the Doublecortin Superfamily

“…Doublecortin domain containing 2 , DCDC2 , has been suggested to play a causative role in reading disabilities and has been implicated as a susceptibility gene for Dyslexia [25,26]. Retinitis Pigmentosa 1 , RP1 , and Retinitis Pigmentosa like 1 , RP1L1 , are associated with inherited blindness [27,28]. The known CNS expression pattern and possible function of the DCX gene superfamily are summarized in Table 1.…”