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The Journal of Dermatology Sep 2019
Topics: Cell Lineage; Child, Preschool; Female; Humans; MART-1 Antigen; Melanocytes; Microphthalmia-Associated Transcription Factor; Piebaldism; Proto-Oncogene Proteins c-kit; Skin; Skin Pigmentation
PubMed: 31254302
DOI: 10.1111/1346-8138.14999 -
American Journal of Medical Genetics.... Dec 2020
Topics: Adolescent; Humans; Male; Mutation; Phenotype; Piebaldism; Snail Family Transcription Factors; Waardenburg Syndrome
PubMed: 32975012
DOI: 10.1002/ajmg.a.61887 -
Clinical and Experimental Dermatology Oct 2020
Topics: Adult; Cell Count; Cell Survival; Epidermal Cells; Female; Humans; Keratinocytes; Male; Melanocytes; Piebaldism; Transplantation, Autologous; Vitiligo
PubMed: 32311146
DOI: 10.1111/ced.14249 -
PloS One 2020Congenital deafness in the domestic dog is usually related to the presence of white pigmentation, which is controlled primarily by the piebald locus on chromosome 20 and...
Congenital deafness in the domestic dog is usually related to the presence of white pigmentation, which is controlled primarily by the piebald locus on chromosome 20 and also by merle on chromosome 10. Pigment-associated deafness is also seen in other species, including cats, mice, sheep, alpacas, horses, cows, pigs, and humans, but the genetic factors determining why some piebald or merle dogs develop deafness while others do not have yet to be determined. Here we perform a genome-wide association study (GWAS) to identify regions of the canine genome significantly associated with deafness in three dog breeds carrying piebald: Dalmatian, Australian cattle dog, and English setter. We include bilaterally deaf, unilaterally deaf, and matched control dogs from the same litter, phenotyped using the brainstem auditory evoked response (BAER) hearing test. Principal component analysis showed that we have different distributions of cases and controls in genetically distinct Dalmatian populations, therefore GWAS was performed separately for North American and UK samples. We identified one genome-wide significant association and 14 suggestive (chromosome-wide) associations using the GWAS design of bilaterally deaf vs. control Australian cattle dogs. However, these associations were not located on the same chromosome as the piebald locus, indicating the complexity of the genetics underlying this disease in the domestic dog. Because of this apparent complex genetic architecture, larger sample sizes may be needed to detect the genetic loci modulating risk in piebald dogs.
Topics: Animals; Case-Control Studies; Deafness; Dog Diseases; Dogs; Evoked Potentials, Auditory; Genetic Loci; Genetic Predisposition to Disease; Genome-Wide Association Study; Hearing Tests; Polymorphism, Single Nucleotide; Selective Breeding; Skin Pigmentation
PubMed: 32413090
DOI: 10.1371/journal.pone.0232900 -
Scientific Reports Apr 2020We have developed a new technique to study the integrity, morphology and functionality of the retinal neurons and the retinal pigment epithelium (RPE). Young and old...
We have developed a new technique to study the integrity, morphology and functionality of the retinal neurons and the retinal pigment epithelium (RPE). Young and old control albino (Sprague-Dawley) and pigmented (Piebald Virol Glaxo) rats, and dystrophic albino (P23H-1) and pigmented (Royal College of Surgeons) rats received a single intravitreal injection of 3% Fluorogold (FG) and their retinas were analyzed from 5 minutes to 30 days later. Retinas were imaged in vivo with SD-OCT and ex vivo in flat-mounts and in cross-sections. Fifteen minutes and 24 hours after intravitreal administration of FG retinal neurons and the RPE, but no glial cells, were labeled with FG-filled vesicles. The tracer reached the RPE 15 minutes after FG administration, and this labeling remained up to 30 days. Tracing for 15 minutes or 24 hours did not cause oxidative stress. Intraretinal tracing delineated the pathological retinal remodelling occurring in the dystrophic strains. The RPE of the P23H-1 strain was highly altered in aged animals, while the RPE of the RCS strain, which is unable to phagocytose, did not accumulate the tracer even at young ages when the retinal neural circuit is still preserved. In both dystrophic strains, the RPE cells were pleomorphic and polymegathic.
Topics: Animals; Cell Tracking; Female; Phagocytosis; Rats; Rats, Sprague-Dawley; Retinal Degeneration; Retinal Neurons; Retinal Pigment Epithelium; Stilbamidines
PubMed: 32350384
DOI: 10.1038/s41598-020-64131-z -
Frontiers in Immunology 2020Griscelli syndrome type 2 (GS-2) is an inborn error of immunity characterized by partial albinism and episodes of hemophagocytic lymphohistiocytosis (HLH). It is caused...
Griscelli syndrome type 2 (GS-2) is an inborn error of immunity characterized by partial albinism and episodes of hemophagocytic lymphohistiocytosis (HLH). It is caused by mutations that encode RAB27A, a member of the Rab GTPase family. RAB27A is expressed in many tissues and regulates vesicular transport and organelle dynamics. Occasionally, GS-2 patients with mutation display normal pigmentation. The study of such variants provides the opportunity to map distinct binding sites for tissue-specific effectors on RAB27A. Here we present a new case of GS-2 without albinism (GS-2 sine albinism) caused by a novel missense mutation (Val143Ala) in the RAB27A and characterize its functional cellular consequences. Using pertinent animal cell lines, the Val143Ala mutation impairs both the RAB27A-SLP2-A interaction and RAB27A-MUNC13-4 interaction, but it does not affect the RAB27A-melanophilin (MLPH)/SLAC2-A interaction that is crucial for skin and hair pigmentation. We conclude that disruption of the RAB27A-MUNC13-4 interaction in cytotoxic lymphocytes leads to the HLH predisposition of the GS-2 patient with the Val143Ala mutation. Finally, we include a review of GS-2 sine albinism cases reported in the literature, summarizing their genetic and clinical characteristics.
Topics: Adaptor Proteins, Signal Transducing; Adolescent; Albinism; Animals; Binding Sites; COS Cells; Cell Line; Child; Child, Preschool; Chlorocebus aethiops; Female; Humans; Infant; Infant, Newborn; Leukocytes, Mononuclear; Lymphohistiocytosis, Hemophagocytic; Male; Membrane Proteins; Mutation, Missense; Piebaldism; Primary Immunodeficiency Diseases; rab GTP-Binding Proteins; rab27 GTP-Binding Proteins
PubMed: 33362801
DOI: 10.3389/fimmu.2020.612977 -
American Journal of Veterinary Research Aug 2022To assess the presence of suspected pigment-associated deafness in North American yaks (Bos grunniens).
OBJECTIVE
To assess the presence of suspected pigment-associated deafness in North American yaks (Bos grunniens).
ANIMALS
12 North American yaks, including 11 with the homozygous piebald Royal pigmentation phenotype and 1 with the heterozygous piebald Trim phenotype.
PROCEDURES
Hearing was assessed using the brainstem auditory evoked response (BAER) on yaks restrained in the head gate of a grooming chute.
RESULTS
Five of the Royal yaks and the Trim yak had hearing in both ears. Six Royal yaks were affected; 3 were deaf in 1 ear and 3 were deaf in both ears.
CLINICAL RELEVANCE
For the first time, probable sensorineural deafness has been confirmed to be present in Royal yaks. The disorder is assumed to be congenital and associated with white pigmentation, based on the pattern of occurrence in other species.
Topics: Animals; Cattle; Cattle Diseases; Deafness; North America; Phenotype; Pigmentation
PubMed: 35914095
DOI: 10.2460/ajvr.22.03.0050 -
G3 (Bethesda, Md.) Jan 2020The body coloration of animals is due to pigment cells derived from neural crest cells, which are multipotent and differentiate into diverse cell types. Medaka ()...
The body coloration of animals is due to pigment cells derived from neural crest cells, which are multipotent and differentiate into diverse cell types. Medaka () possesses four distinct types of pigment cells known as melanophores, xanthophores, iridophores, and leucophores. The () mutant of medaka is characterized by reduced numbers of melanophores and leucophores. We here identify () as the gene whose mutation gives rise to the phenotype. This identification was confirmed by generation of knockout medaka and the findings that these fish also manifest reduced numbers of melanophores and leucophores and fail to rescue the mutant phenotype. We also found that expression of , , , and genes is down-regulated in both and knockout medaka, implicating c-Kit signaling in regulation of the expression of these genes as well as the encoded transcription factors in pigment cell specification. Our results may provide insight into the pathogenesis of c-Kit-related pigmentation disorders such as piebaldism in humans, and our knockout medaka may prove useful as a tool for drug screening.
Topics: Animals; Fish Proteins; Melanophores; Microphthalmia-Associated Transcription Factor; Mutation; Oryzias; PAX7 Transcription Factor; SOXD Transcription Factors; Skin Pigmentation; Stem Cell Factor
PubMed: 31757930
DOI: 10.1534/g3.119.400561 -
BMC Genomics Jun 2021Copper was used for many years in aquaculture operations as an effective algaecide or a parasite treatment of fish. It is an essential nutrient with numerous functions...
BACKGROUND
Copper was used for many years in aquaculture operations as an effective algaecide or a parasite treatment of fish. It is an essential nutrient with numerous functions in organisms, but is toxic at high concentrations. However, the toxicity of copper to fish remains unclear. In this study, we used the piebald naked carp, Gymnocypris eckloni, as a model. RNA-seq data from different tissues, including gills, kidney, and liver, were used to investigate the underlying mechanism of copper toxicology in G. eckloni.
RESULTS
We compared the transcriptomes from different tissues with different time durations of copper ion treatment. After 72 h copper ion treatment, the number of genes with different expression in gills and liver changed dramatically, but not in kidneys. In KEGG functional enrichment, the pattern of differentially expressed genes (DEGs) was also similar in the gills and liver. The most enriched pathway of DEGs was "Ribosome" in both tissues. Furthermore, we analyzed the expression levels of genes involved in oxidative stress response and protein synthesis using qPCR and RNA-seq data. Our results showed that several genes involved in oxidative stress response were up-regulated both in gills and liver. Up-regulation of these genes indicated that copper treatment caused oxidative stress, which is likely to result in ribosome damage. In addition, our results showed that the expression of Eef1b2, a transcription elongation factor, was decreased in the liver under oxidative stress, and the expression of translation initiation factors Eif4ebp1 and eIF2α, and elongation factor eEF2 was up-regulated. These results supported the idea that oxidative stress inhibits protein synthesis in cells.
CONCLUSIONS
Our results indicate that copper exposure caused different responses in different tissues, since the gene expression patterns changed substantially either in the gills or liver, while the effect on the kidney was relatively weak. Furthermore, our results indicated that the expression pattern of the genes involved in the ribosome, which is a complex molecular machine orchestrating protein synthesis in the cell, together with translation initiation factor and elongation factors, were affected by copper exposure both in the gills and liver of piebald naked carp. This result leads us to speculate that the downregulation of global protein synthesis is an acute response strategy of fish to metal-induced oxidative stress. Moreover, we speculate that this strategy not only exists in the selective translation of proteins but also exists in the specific translation of functional proteins in tissues and cells.
Topics: Animals; Carps; Copper; Gene Expression Profiling; Gills; Transcriptome
PubMed: 34090338
DOI: 10.1186/s12864-021-07673-4 -
Skin Research and Technology : Official... Jan 2024To compare the efficacy and safety of autologous cultured melanocytes transplantation (CMT) and non-cultured epidermal cell suspension transplantation (NCES) in the...
Comparative outcomes of autologous cultured melanocytes transplantation and non-cultured epidermal cell suspension transplantation in piebaldism patients: A retrospective study.
PURPOSE
To compare the efficacy and safety of autologous cultured melanocytes transplantation (CMT) and non-cultured epidermal cell suspension transplantation (NCES) in the treatment of piebaldism.
PATIENTS AND METHODS
A retrospective study was conducted on 30 anatomically based lesions from nine piebaldism patients who underwent either CMT (n = 7) or NCES (n = 23) between 2018 and 2020. The extent of repigmentation and colour matching was evaluated in all recipient sites using a digital imaging analysis system. In addition, adverse effects have also been assessed by follow-up results.
RESULTS
More than 75% repigmentation was achieved in 100% (7/7) and 60.9% (14/23) of the 30 lesions with the CMT and NCES, respectively. There were significant differences between the two methods in terms of repigmentation. The majority of patients had colour mismatches, and there was no discernible difference between the two surgical techniques. Adverse reactions rarely occurred.
CONCLUSION
The present study suggested that autologous CMT may provide better repigmentation in piebaldism patients than NCES with no significant side effects.
Topics: Humans; Retrospective Studies; Piebaldism; Treatment Outcome; Vitiligo; Melanocytes
PubMed: 38225879
DOI: 10.1111/srt.13580