-
Journal of Fish Biology Jan 2023Hypomelanosis refers to a suite of skin pigment abnormalities, including albinism, leucism and piebaldism. While documented across many vertebrate species, examples of...
Hypomelanosis refers to a suite of skin pigment abnormalities, including albinism, leucism and piebaldism. While documented across many vertebrate species, examples of hypomelanosis are rarely seen in chondrichthyans, with little insight into the potential effects on survival. Here, we report the first observation of abnormal skin pigmentation indicative of piebaldism in the Atlantic nurse shark Ginglymostoma cirratum, representing only the second reported case of skin aberrations for this species. This extremely rare observation is discussed in the broader context of fitness variation and long-term survival.
Topics: Animals; Piebaldism; Sharks
PubMed: 36196931
DOI: 10.1111/jfb.15238 -
Journal of Chemical Theory and... Oct 2022KIT is a type 3 receptor tyrosine kinase that plays a crucial role in cellular growth and proliferation. Mutations in KIT can dysregulate its active-inactive...
KIT is a type 3 receptor tyrosine kinase that plays a crucial role in cellular growth and proliferation. Mutations in KIT can dysregulate its active-inactive equilibrium. Activating mutations drive cancer growth, while deactivating mutations result in the loss of skin and hair pigmentation in a disease known as piebaldism. Here, we propose a method based on molecular dynamics and free energy calculations to predict the functional effect of KIT mutations. Our calculations may have important clinical implications by defining the functional significance of previously uncharacterized KIT mutations and guiding targeted therapy.
Topics: Humans; Mutation; Piebaldism; Proto-Oncogene Mas; Proto-Oncogene Proteins c-kit
PubMed: 36166736
DOI: 10.1021/acs.jctc.2c00526 -
Scientific Reports Sep 2022While it is well-established that bone responds dynamically to mechanical loading, the effects of mild traumatic brain injury (mTBI) on cranial bone composition are...
While it is well-established that bone responds dynamically to mechanical loading, the effects of mild traumatic brain injury (mTBI) on cranial bone composition are unclear. We hypothesized that repeated mTBI (rmTBI) would change the microstructure of cranial bones, without gross skull fractures. To address this, young adult female Piebald Viral Glaxo rats received sham, 1×, 2× or 3× closed-head mTBIs delivered at 24 h intervals, using a weight-drop device custom-built for reproducible impact. Skull bones were collected at 2 or 10 weeks after the final injury/sham procedure, imaged by micro computed tomography and analyzed at predetermined regions of interest. In the interparietal bone, proximal to the injury site, modest increases in bone thickness were observed at 2 weeks, particularly following 2× and 3× mTBI. By 10 weeks, 2× mTBI induced a robust increase in the volume and thickness of the interparietal bone, alongside a corresponding decrease in the volume of marrow cavities in the diploë region. In contrast, neither parietal nor frontal skull samples were affected by rmTBI. Our findings demonstrate time- and location-dependent effects of rmTBI on cranial bone structure, highlighting a need to consider microstructural alterations to cranial bone when assessing the consequences of rmTBI.
Topics: Animals; Brain Concussion; Brain Injuries, Traumatic; Disease Models, Animal; Female; Rats; Skull; Time; X-Ray Microtomography
PubMed: 36050485
DOI: 10.1038/s41598-022-18643-5 -
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 -
Journal of the European Academy of... Sep 2022Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2,...
BACKGROUND
Pathogenic variants in KITLG, a crucial protein involved in pigmentation and neural crest cell migration, cause non-syndromic hearing loss, Waardenburg syndrome type 2, familial progressive hyperpigmentation and familial progressive hyper- and hypopigmentation, all of which are inherited in an autosomal dominant manner.
OBJECTIVES
To describe the genotypic and clinical spectrum of biallelic KITLG-variants.
METHODS
We used a genotype-first approach through the GeneMatcher data sharing platform to collect individuals with biallelic KITLG variants and reviewed the literature for overlapping reports.
RESULTS
We describe the first case series with biallelic KITLG variants; we expand the known hypomelanosis spectrum to include a 'sock-and-glove-like', symmetric distribution, progressive repigmentation and generalized hypomelanosis. We speculate that KITLG biallelic loss-of-function variants cause generalized hypomelanosis, whilst variants with residual function lead to a variable auditory-pigmentary disorder mostly reminiscent of Waardenburg syndrome type 2 or piebaldism.
CONCLUSIONS
We provide consolidating evidence that biallelic KITLG variants cause a distinct auditory-pigmentary disorder. We evidence a significant clinical variability, similar to the one previously observed in KIT-related piebaldism.
Topics: Hearing Loss, Sensorineural; Humans; Hyperpigmentation; Hypopigmentation; Piebaldism; Stem Cell Factor; Waardenburg Syndrome
PubMed: 35543077
DOI: 10.1111/jdv.18207 -
BMC Genomics Apr 2022Leaf colour mutations are universally expressed at the seedling stage and are ideal materials for exploring the chlorophyll biosynthesis pathway, carotenoid metabolism...
BACKGROUND
Leaf colour mutations are universally expressed at the seedling stage and are ideal materials for exploring the chlorophyll biosynthesis pathway, carotenoid metabolism and the flavonoid biosynthesis pathway in plants.
RESULTS
In this research, we analysed the different degrees of albinism in apple (Malus domestica) seedlings, including white-leaf mutants (WM), piebald leaf mutants (PM), light-green leaf mutants (LM) and normal leaves (NL) using bisulfite sequencing (BS-seq) and RNA sequencing (RNA-seq). There were 61,755, 79,824, and 74,899 differentially methylated regions (DMRs) and 7566, 3660, and 3546 differentially expressed genes (DEGs) identified in the WM/NL, PM/NL and LM/NL comparisons, respectively.
CONCLUSION
The analysis of the methylome and transcriptome showed that 9 DMR-associated DEGs were involved in the carotenoid metabolism and flavonoid biosynthesis pathway. The expression of different transcription factors (TFs) may also influence the chlorophyll biosynthesis pathway, carotenoid metabolism and the flavonoid biosynthesis pathway in apple leaf mutants. This study provides a new method for understanding the differences in the formation of apple seedlings with different degrees of albinism.
Topics: Albinism; Carotenoids; Chlorophyll; Epigenome; Flavonoids; Gene Expression Profiling; Gene Expression Regulation, Plant; Malus; Plant Leaves; Seedlings; Transcriptome
PubMed: 35439938
DOI: 10.1186/s12864-022-08535-3 -
Journal of Visualized Experiments : JoVE Mar 2022Melanocytes are specialized neural crest-derived cells present in the epidermal skin. These cells synthesize melanin pigment that protects the genome from harmful...
Melanocytes are specialized neural crest-derived cells present in the epidermal skin. These cells synthesize melanin pigment that protects the genome from harmful ultraviolet radiations. Perturbations in melanocyte functioning lead to pigmentary disorders such as piebaldism, albinism, vitiligo, melasma, and melanoma. Zebrafish is an excellent model system to understand melanocyte functions. The presence of conspicuous pigmented melanocytes, ease of genetic manipulation, and availability of transgenic fluorescent lines facilitate the study of pigmentation. This study employs the use of wild-type and transgenic zebrafish lines that drive green fluorescent protein (GFP) expression under mitfa and tyrp1 promoters that mark various stages of melanocytes. Morpholino-based silencing of candidate genes is achieved to evaluate the phenotypic outcome on larval pigmentation and is applicable to screen for regulators of pigmentation. This protocol demonstrates the method from microinjection to imaging and fluorescence-activated cell sorting (FACS)-based dissection of phenotypes using two candidate genes, carbonic anhydrase 14 (Ca14) and a histone variant (H2afv), to comprehensively assess the pigmentation outcome. Further, this protocol demonstrates segregating candidate genes into melanocyte specifiers and differentiators that selectively alter melanocyte numbers and melanin content per cell, respectively.
Topics: Animals; Melanocytes; Pigmentation; Pigmentation Disorders; Reverse Genetics; Zebrafish
PubMed: 35312674
DOI: 10.3791/62955 -
Chaos (Woodbury, N.Y.) Jan 2022The classical Turing mechanism containing a long-range inhibition and a short-range self-enhancement provides a type of explanation for the formation of patterns on body...
The classical Turing mechanism containing a long-range inhibition and a short-range self-enhancement provides a type of explanation for the formation of patterns on body surfaces of some vertebrates, e.g., zebras, giraffes, and cheetahs. For other type of patterns (irregular spots) on body surfaces of some vertebrates, e.g., loaches, finless eels, and dalmatian dogs, the classical Turing mechanism no longer applies. Here, we propose a mechanism, i.e., the supercritical pitchfork bifurcation, which may explain the formation of this type of irregular spots, and present a method to quantify the similarity of such patterns. We assume that, under certain conditions, the only stable state of "morphogen" loses its stability and transitions to two newly generated stable states with the influence of external noise, thus producing such ruleless piebald patterns in space. The difference between the competitiveness of these two states may affect the resulting pattern. Moreover, we propose a mathematical model based on this conjecture and obtain this type of irregular patterns by numerical simulation. Furthermore, we also study the influence of parameters in the model on pattern structures and obtain the corresponding pattern structures of some vertebrates in nature, which verifies our conjecture.
Topics: Animals; Computer Simulation; Dogs; Models, Biological; Models, Theoretical; Vertebrates
PubMed: 35105114
DOI: 10.1063/5.0070325 -
Annals of Laboratory Medicine May 2022
Topics: Humans; Lymphohistiocytosis, Hemophagocytic; Piebaldism; Primary Immunodeficiency Diseases; Republic of Korea
PubMed: 34907113
DOI: 10.3343/alm.2022.42.3.384 -
Genes Sep 2021A 1-month-old, female, smooth-haired miniature Dachshund with dilute color and neurological defects was investigated. The aim of this study was to characterize the...
A 1-month-old, female, smooth-haired miniature Dachshund with dilute color and neurological defects was investigated. The aim of this study was to characterize the clinical signs, histopathological changes and underlying genetic defect. The puppy had visible coat color dilution and was unable to hold its head on its own or to remain in a stable prone position for an extended period. Histopathological examination revealed an accumulation of clumped melanin and deposition of accumulated keratin within the hair follicles, accompanied by dermal pigmentary incontinence. These dermatological changes were compatible with the histopathology described in dogs with an -related dilute coat color. We sequenced the genome of the affected dog and compared the data to 795 control genomes. , coding for myosin VA, was investigated as the top functional candidate gene. This search revealed a private homozygous frameshift variant in , XM_022412522.1:c.4973_4974insA, predicted to truncate 269 amino acids (13.8%) of the wild type myosin VA protein, XP_022268230.1:p.(Asn1658Lysfs*28). The genotypes of the index family showed the expected co-segregation with the phenotype and the mutant allele was absent from 142 additionally genotyped, unrelated Dachshund dogs. loss of function variants cause Griscelli type 1 syndrome in humans, lavender foal in horses and the phenotype of the mouse mutant. Based on the available data, together with current knowledge on other species, we propose the identified frameshift insertion as a candidate causative variant for the observed dermatological and neurological signs in the investigated dog.
Topics: Alleles; Animals; Dog Diseases; Dogs; Frameshift Mutation; Genetic Predisposition to Disease; Genotype; Hair Color; Hearing Loss, Sensorineural; Homozygote; Humans; Myosin Heavy Chains; Myosin Type V; Phenotype; Piebaldism; Pigmentation; Pigmentation Disorders
PubMed: 34680875
DOI: 10.3390/genes12101479