SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans

  title={SLC24A5, a Putative Cation Exchanger, Affects Pigmentation in Zebrafish and Humans},
  author={Rebecca L. Lamason and Manzoor-Ali P.K. Mohideen and Jason R Mest and Andrew C. Wong and Heather L. Norton and Michele C Aros and Michael J. Jurynec and Xianyun Mao and Vanessa R. Humphreville and Jasper E. Humbert and Soniya Sinha and Jessica L. Moore and Pudur Jagadeeswaran and Wei Zhao and Gang Ning and Izabela Makałowska and Paul M. McKeigue and David O'donnell and Rick A. Kittles and Esteban Juan Parra and Nancy J. Mangini and David Jonah Grunwald and Mark David Shriver and Victor A. Canfield and Keith C. Cheng},
  pages={1782 - 1786}
Lighter variations of pigmentation in humans are associated with diminished number, size, and density of melanosomes, the pigmented organelles of melanocytes. Here we show that zebrafish golden mutants share these melanosomal changes and that golden encodes a putative cation exchanger slc24a5 (nckx5) that localizes to an intracellular membrane, likely the melanosome or its precursor. The human ortholog is highly similar in sequence and functional in zebrafish. The evolutionarily conserved… 
Slc45a2 and V‐ATPase are regulators of melanosomal pH homeostasis in zebrafish, providing a mechanism for human pigment evolution and disease
It is shown that it is possible to rescue the melanization potential of the albino melanosomes through genetic and chemical inhibition of V‐ATPase, thereby increasing internal melanosome pH.
Repression of Slc24a5 can reduce pigmentation in chicken.
Results show that down-regulation of Slc24a5 results in a reduction of melanin content, as well as a decrease of melaeneous type β and type χ melanosomes simultaneously, suggesting that Slc 24a5 function is conserved in the chicken, and necessary for melanin synthesis.
Identification of polymorphism in the SCL24A5 gene of cattle
The SLC24A5 gene in cattle with light and dark skin pigmentation was investigated and sixteen SNPs identified, all of which were polymorphic between Bos taurus, Bos indicus and Sanga, while none of them resulted associated with the studied phenotype.
A golden age of human pigmentation genetics.
  • R. Sturm
  • Biology
    Trends in genetics : TIG
  • 2006
A functional approach to understanding the role of NCKX5 in Xenopus pigmentation
Xenopus laevis is employed as an in vivo model system to further investigate the function of NCKX5 in pigmentation and suggest NCKx5 may have an alternative activity that is key to its role in the regulation of pigmentation.
SLC24A5: exchanging genetic and biochemical knowledge
Combining the extensive work in model organisms, genetic linkage, population variation, and signatures of selection provide compelling evidence for functional effects of SLC24A5 and more specifically rs1426654, on pigmentation.
Population differences of two coding SNPs in pigmentation-related genes SLC24A5 and SLC45A2
New allelic data for these two genes SLC24A5 and SLC45A2 are generated from samples of Chinese, Uygurs, Ghanaians,South African Xhosa, South African Europeans, and Sri Lankans and it is demonstrated that the SLC 45A2 allele is a more specific AIM than the S LC24A 5 allele because the former clearly distinguishes the Sri Lankan from the Europeans.
Functional Assessment of Human Coding Mutations Affecting Skin Pigmentation Using Zebrafish
The experimental conclusion that E272K is unlikely to affect pigmentation is consistent with a lack of correlation between this polymorphism and quantitatively measured skin color in 59 East Asian humans, and may potentially contribute to the understanding of the functional relationships between DNA sequence variation, human biology, and disease.
Molecular characterization of SLC24A5 variants and evaluation of Nitisinone treatment efficacy in a zebrafish model of OCA6
Two new variants of SLC24A5 cosegregating with the OCA phenotype are identified, including nystagmus, strabismus, foveal hypoplasia, albinotic fundus, and vision impairment, in three large consanguineous Pakistani families, and treatment with nitisinone is unlikely to be therapeutic in OCA6 patients.
N-Ethylmaleimide-Sensitive Factor b (nsfb) Is Required for Normal Pigmentation of the Zebrafish Retinal Pigment Epithelium.
PURPOSE Despite the number of albinism-causing mutations identified in human patients and animal models, there remain a significant number of cases for which no mutation has been identified,


Mutations in the gene encoding B, a novel transporter protein, reduce melanin content in medaka
The first successful positional cloning of a medaka gene (AIM1): one that encodes a transporter that mediates melanin synthesis, which is predicted to consist of 12 transmembrane domains and is 55% identical to a human EST of unknown function isolated from melanocytes and melanoma cells.
Single nucleotide polymorphisms in the MATP gene are associated with normal human pigmentation variation
The role of two nonpathogenic nonsynonymous single nucleotide polymorphisms in the MATP gene are investigated to determine if they are associated with normal human skin, hair, and eye color variation and results indicate that the allele frequencies of both polymorphisms are significantly different between population groups.
Characterization of melanosomes in murine Hermansky-Pudlak syndrome: mechanisms of hypopigmentation.
It is demonstrated that all strains examined here except for ashen have defects in morphogenesis, the most severely affected is sandy, muted, and buff followed by subtle gray, and aberrant biogenesis of melanosomes may play a part in the pathogenesis of pigmentary glaucoma observed in these mice.
Melanosome morphologies in murine models of hermansky-pudlak syndrome reflect blocks in organelle development.
The morphology of the melanosomes in the skin of 10 of the mutant mouse Hermansky-Pudlak syndrome strains is examined by transmission electron microscopy and it is demonstrated that the morphologies reflect inhibition of organelle maturation or transfer.
The 8818G allele of the agouti signaling protein (ASIP) gene is ancestral and is associated with darker skin color in African Americans
This study suggests that the ASIP G>A polymorphism exhibits a dominant effect leading to lighter skin color and that variation in the AsIP gene may have been one of several factors contributing to reductions in pigmentation in some populations.
Regulation of Tyrosinase Processing and Trafficking by Organellar pH and by Proteasome Activity*
It is shown that TYR can be released from the ER in the presence of protonophore or proton pump inhibitors which increase the pH of intracellular organelles, after which TYR is transported correctly to the Golgi, and then to melanosomes via the endosomal sorting system.
Sequences associated with human iris pigmentation.
The results suggest that cryptic population structure might serve as a leverage tool for complex trait gene mapping if genomes are screened with the appropriate ancestry informative markers.
Effective targeted gene ‘knockdown’ in zebrafish
It is shown here that antisense, morpholino-modified oligonucleotides (morpholinos) are effective and specific translational inhibitors in zebrafish, and conserved vertebrate processes and diseases are now amenable to a systematic, in vivo, reverse-genetic paradigm using zebra fish embryos.