scholarly journals A KRT71 Loss-of-Function Variant Results in Inner Root Sheath Dysplasia and Recessive Congenital Hypotrichosis of Hereford Cattle

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 1038
Author(s):  
Joana G. P. Jacinto ◽  
Alysta D. Markey ◽  
Inês M. B. Veiga ◽  
Julia M. Paris ◽  
Monika Welle ◽  
...  
Keyword(s):  
Hair Follicle ◽  
The Body ◽  
Large Animal ◽  
Type Ii ◽  
Loss Of Function ◽  
Positional Candidate ◽  
Root Sheath ◽  
Hereford Cattle ◽  
A Genome ◽  
Inner Root Sheath

Genodermatoses, such as heritable skin disorders, mostly represent Mendelian conditions. Congenital hypotrichosis (HY) characterize a condition of being born with less hair than normal. The purpose of this study was to characterize the clinicopathological phenotype of a breed-specific non-syndromic form of HY in Hereford cattle and to identify the causative genetic variant for this recessive disorder. Affected calves showed a very short, fine, wooly, kinky and curly coat over all parts of the body, with a major expression in the ears, the inner part of the limbs, and in the thoracic-abdominal region. Histopathology showed a severely altered morphology of the inner root sheath (IRS) of the hair follicle with abnormal Huxley and Henle’s layers and severely dysplastic hair shafts. A genome-wide association study revealed an association signal on chromosome 5. Homozygosity mapping in a subset of cases refined the HY locus to a 690 kb critical interval encompassing a cluster of type II keratin encoding genes. Protein-coding exons of six positional candidate genes with known hair or hair follicle function were re-sequenced. This revealed a protein-changing variant in the KRT71 gene that encodes a type II keratin specifically expressed in the IRS of the hair follicle (c.281delTGTGCCCA; p.Met94AsnfsX14). Besides obvious phenocopies, a perfect concordance between the presence of this most likely pathogenic loss-of-function variant located in the head domain of KRT71 and the HY phenotype was found. This recessive KRT71-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002114-9913).

scholarly journals A Nonsense Variant in Hephaestin Like 1 (HEPHL1) Is Responsible for Congenital Hypotrichosis in Belted Galloway Cattle

Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 643
Author(s):  
Thibaud Kuca ◽  
Brandy M. Marron ◽  
Joana G. P. Jacinto ◽  
Julia M. Paris ◽  
Christian Gerspach ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Homozygosity Mapping ◽  
Mendelian Inheritance ◽  
Large Animal Model ◽  
Large Animal ◽  
Loss Of Function ◽  
Protein Coding ◽  
Positional Candidate ◽  
Genome Wide ◽  
A Genome

Genodermatosis such as hair disorders mostly follow a monogenic mode of inheritance. Congenital hypotrichosis (HY) belong to this group of disorders and is characterized by abnormally reduced hair since birth. The purpose of this study was to characterize the clinical phenotype of a breed-specific non-syndromic form of HY in Belted Galloway cattle and to identify the causative genetic variant for this recessive disorder. An affected calf born in Switzerland presented with multiple small to large areas of alopecia on the limbs and on the dorsal part of the head, neck, and back. A genome-wide association study using Swiss and US Belted Galloway cattle encompassing 12 cases and 61 controls revealed an association signal on chromosome 29. Homozygosity mapping in a subset of cases refined the HY locus to a 1.5 Mb critical interval and subsequent Sanger sequencing of protein-coding exons of positional candidate genes revealed a stop gain variant in the HEPHL1 gene that encodes a multi-copper ferroxidase protein so-called hephaestin like 1 (c.1684A>T; p.Lys562*). A perfect concordance between the homozygous presence of this most likely pathogenic loss-of-function variant and the HY phenotype was found. Genotyping of more than 700 purebred Swiss and US Belted Galloway cattle showed the global spread of the mutation. This study provides a molecular test that will permit the avoidance of risk matings by systematic genotyping of relevant breeding animals. This rare recessive HEPHL1-related form of hypotrichosis provides a novel large animal model for similar human conditions. The results have been incorporated in the Online Mendelian Inheritance in Animals (OMIA) database (OMIA 002230-9913).

A Selectable Biomarker in Hair Follicle Cycles – Cathepsins: A Preliminary Study in Murine

2021 ◽  
pp. 1-7
Author(s):  
Jingzhu Bai ◽  
Zijian Gong ◽  
Qingfang Xu ◽  
Haiyan Chen ◽  
Qiaoping Chen ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Hair Cycle ◽  
Biological Factors ◽  
Outer Root Sheath ◽  
Physiological Processes ◽  
Intervention Measures ◽  
Root Sheath ◽  
Inner Root Sheath ◽  
Preliminary Study ◽  
Paraffin Method

<b><i>Background/Objective:</i></b> Hair cycle is regulated by many biological factors. Cathepsins are involved in various physiological processes in human skin. Here, we investigated the cathepsin expression and distribution changes in follicular growth cycles for better understanding the hair cycles and to explore new intervention measures. <b><i>Methods:</i></b> The 24 mice (C57BL/6, female, 7-week old) were selected and removed the back hair via rosin/paraffin method. At Day 8, Day 20, and Day 25, biopsy on post-plucking area was done. Immunohistochemical staining, Western blot, and Q-PCR were used to test the cathepsin B/D/L/E. <b><i>Results:</i></b> In anagen, cathepsins (B, D, L, and E) were distributed in the hair follicle matrix, inner hair root sheath, and hair. In catagen, cathepsins were mainly observed in un-apoptosis inner root sheath and outer root sheath. Expression of cathepsins B-mRNA and L-mRNA was decreased from anagen and catagen to telogen. Cathepsin D-mRNA was increased in catagen and then decreased in telogen. Cathepsin E-mRNA was decreased in catagen and slightly increased in telogen. <b><i>Conclusions:</i></b> The distribution and expression of cathepsins B, D, L, and E in hair follicle changed with hair growth process which indicated that cathepsins might act as selectable biomarkers of hair cycle in different stages.

scholarly journals THE ELECTRON MICROSCOPY OF THE HUMAN HAIR FOLLICLE

1957 ◽  
Vol 3 (2) ◽  
pp. 223-230 ◽  
Author(s):  
M. S. C. Birbeck ◽  
E. H. Mercer
Keyword(s):  
Hair Follicle ◽  
Cross Sections ◽  
Plasma Membranes ◽  
Membrane Complex ◽  
Outer Sheath ◽  
Root Sheath ◽  
Inner Root Sheath ◽  
Cell Layers ◽  
Adhesive Contacts ◽  
Similar Complex

1. The three cylinders of cells, each one cell thick, which together constitute the inner root sheath, arise from the peripheral portions of the undifferentiated matrix. These cells, like the hair cuticle, are stabilised by the spread of adhesive contacts between their plasma membranes which occurs in the mid-bulb and upper bulb of the hair follicle. 2. The characteristic intracellular product of all three cell layers is trichohyaline. This substance is formed in the first place as amorphous droplets which subsequently transform into a birefringent form. 3. This transformation, involving the formation of a birefringent product from an amorphous precursor, is in contrast to the formation in the cortex of keratin which originates in a fibrous form. 4. Trichohyaline appears first and transforms first in the cells of Henle which are nearest the outer sheath and the dermal supply vessels. This transformation occurs at the level of the neck of the follicle. Synthesis and transformation in the cells of Huxley and the sheath cuticle lag behind the similar events in the cells of Henle. The transformation does not begin until the lower prekeratinous zone in the Huxley and cuticle cells. 5. The amorpous-fibrous transformation occurs rapidly cell by cell and involves the conversion of all the trichohyaline droplets. In longitudinal sections the birefringent modification can be seen extending from the droplets in both directions parallel to the axis of the hair. In cross-sections the images of the transformed material are difficult to interpret. They may be seen as sections of corrugated sheets (∼100 A thick) or condensed fibrils ∼100 A in width. 6. At the same time that the trichohyaline transforms, the spacing between the cell membranes increases and a dark deposit appears centrally between them. This membrane complex, and the similar complex of the hair cuticle cells described in Part 2, may be specialised formations whose purpose is to hold the hardened cells together.

Synthesis of porcine pCLCA2 protein during late differentiation of keratinocytes of epidermis and hair follicle inner root sheath

2012 ◽  
Vol 350 (3) ◽  
pp. 445-453 ◽  
Author(s):  
Stephanie Plog ◽  
Lars Mundhenk ◽  
Lutz Langbein ◽  
Achim D. Gruber
Keyword(s):  
Hair Follicle ◽  
Root Sheath ◽  
Inner Root Sheath

scholarly journals 889 Trpv3 gain-of-function mutation impairs differentiation of hair follicle inner root sheath

2019 ◽  
Vol 139 (5) ◽  
pp. S154
Author(s):  
Z. Song ◽  
X. Chen ◽  
Q. Zhao ◽  
Z. Lin ◽  
S. Yang ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Gain Of Function ◽  
Root Sheath ◽  
Inner Root Sheath

scholarly journals Defining BMP functions in the hair follicle by conditional ablation of BMP receptor IA

2003 ◽  
Vol 163 (3) ◽  
pp. 609-623 ◽  
Author(s):  
Krzysztof Kobielak ◽  
H. Amalia Pasolli ◽  
Laura Alonso ◽  
Lisa Polak ◽  
Elaine Fuchs
Keyword(s):  
Hair Follicle ◽  
Progenitor Cells ◽  
Gene Targeting ◽  
Transcriptional Activation ◽  
Hair Shaft ◽  
Bmp Receptor ◽  
Root Sheath ◽  
Inner Root Sheath ◽  
Conditional Gene Targeting ◽  
Sequential Inhibition

Using conditional gene targeting in mice, we show that BMP receptor IA is essential for the differentiation of progenitor cells of the inner root sheath and hair shaft. Without BMPRIA activation, GATA-3 is down-regulated and its regulated control of IRS differentiation is compromised. In contrast, Lef1 is up-regulated, but its regulated control of hair differentiation is still blocked, and BMPRIA-null follicles fail to activate Lef1/β-catenin–regulated genes, including keratin genes. Wnt-mediated transcriptional activation can be restored by transfecting BMPRIA-null keratinocytes with a constitutively activated β-catenin. This places the block downstream from Lef1 expression but upstream from β-catenin stabilization. Because mice lacking the BMP inhibitor Noggin fail to express Lef1, our findings support a model, whereby a sequential inhibition and then activation of BMPRIA is necessary to define a band of hair progenitor cells, which possess enough Lef1 and stabilized β-catenin to activate the hair specific keratin genes and generate the hair shaft.

scholarly journals Refined Immunochemical Characterization in Healthy Dog Skin of the Epidermal Cornification Proteins, Filaggrin, and Corneodesmosin

2018 ◽  
Vol 67 (2) ◽  
pp. 85-97 ◽  
Author(s):  
Didier Pin ◽  
Valérie Pendaries ◽  
Sokhna Keita Alassane ◽  
Carine Froment ◽  
Nicolas Amalric ◽  
...  
Keyword(s):  
Risk Factors ◽  
Genetic Risk ◽  
Genomic Dna ◽  
Dna Analysis ◽  
Hair Follicles ◽  
Loss Of Function ◽  
Lamellar Bodies ◽  
Root Sheath ◽  
Inner Root Sheath ◽  
Cornified Layer

Filaggrin (FLG) and corneodesmosin (CDSN) are two key proteins of the human epidermis. FLG loss-of-function mutations are the strongest genetic risk factors for human atopic dermatitis. Studies of the epidermal distribution of canine FLG and CDSN are limited. Our aim was to better characterize the distribution of FLG and CDSN in canine skin. Using immunohistochemistry on beagle skin, we screened a series of monoclonal antibodies (mAbs) specific for human FLG and CDSN. The cross-reactive mAbs were further used using immunoelectron microscopy and Western blotting. The structure of canine CDSN and FLG was determined using publicly available databases. In the epidermis, four anti-FLG mAbs stained keratohyalin granules in the granular keratinocytes and corneocyte matrix of the lower cornified layer. In urea-extracts of dog epidermis, several bands corresponding to proFLG and FLG monomers were detected. One anti-CDSN mAb stained the cytoplasm of granular keratinocytes and cells of both the inner root sheath and medulla of hair follicles. Dog CDSN was located in lamellar bodies, in the extracellular parts of desmosomes and in corneodesmosomes. A protein of 52 kDa was immunodetected. Genomic DNA analysis revealed that the amino acid sequence and structure of canine and human CDSN were highly similar.

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