Mast cell hyperplasia in the skin of Dsg4-deficient hypotrichosis mice, which are long-living mutants of lupus-prone mice

Abstract

Desmosomal cadherins are essential cell adhesion molecules expressed in the epidermis. We identified a mutation of a cadherin superfamily member, namely, desmoglein 4 (Dsg4), in early onset of death (EOD)( hage ) mice with hypotrichosis. The mutation was induced by the insertion of an early transposon II-beta into intron 8 of Dsg4. Mast cell hyperplasia was observed in the skin of EOD( hage ) mice. The abnormally expanded population of lpr T cells, i.e., CD4(-)CD8(-)B220(+)Thy1.2(+) alphabetaT cells, in the splenocytes of EOD mice was reduced in EOD( hage ) mice. Therefore, it was suspected that the long-living mutant EOD( hage ) mice were selected from lupus-prone EOD mice because of their immunological immaturity. These findings clearly indicate that Dsg4 is an important molecule for the formation of hair follicles and hypothesize that unorganized hyperplastic hair follicles in anagen due to the Dsg4 mutation provide niches for mast cell precursors in the skin.

Identification of IGF1, SLC4A4, WWOX, and SFMBT1 as Hypertension Susceptibility Genes in Han Chinese with a Genome-Wide Gene-Based Association Study

“…CYP7B1 on 8q21.3 is associated with lipoproteins in humans [65] and is associated with abnormal cholesterol homeostasis in mice [66]. FAS on 10q24.1 is associated with hypertension [67], decreased body size, and increased body weight in mice [68], [69]. These SNPs may exert their effects via mechanisms other than by varying gene expression.…”

A guide for building biological pathways along with two case studies: hair and breast development

“…DSG4 protein is expressed in the more highly differentiated layers of the epidermis. It is an important adhesion molecule maintaining the integrity of the hair shaft [91,92]. Multiple transcriptional factors seem to aim for Dsg4 production.…”

Identification of complete linkage disequilibrium in the DSG4 gene and its association with wool length and crimp in Chinese indigenous sheep

“…DSG4 plays an important role in regulating the development and differentiation of hair follicles (Owens et al, 2008;Zhang et al, 2008;Bazzi et al, 2009). Since the discovery of this gene (Kljuic et al, 2003), a number of mutations in the DSG4 gene have been reported to induce a group of hair disorders in mammals (Zhang et al, 2008;Amagai, 2010;El-Amraoui and Petit, 2010); thus, this gene may be considered as a potential candidate that influences wool traits. The human DSG4 is composed of 5 homologous extracellular domains, a transmembrane domain, and a carboxy-terminal cytoplasmic tail (Whittock and Bower, 2003).…”

“…In mice, desmoglein genes are composed of a group of 6 members, including DSG1-6, whereas DSG5 and DSG6 are not found in human or rat genomes (Zhang et al, 2008). A series of sequence variants of the DSG4 gene have been reported to induce lanceolate hair in mice and rats (Meyer et al, 2004;Zhang et al, 2008). More recently, DSG4 gene mutations were found to be associated with human monilethrix hairs (Shimomura et al, 2006;Amagai, 2010).…”

“…These cell-cell junctions are characterized by the presence of desmosomal cadherins, termed as desmogleins and desmocollins (Simpson et al, 2011). In mice, desmoglein genes are composed of a group of 6 members, including DSG1-6, whereas DSG5 and DSG6 are not found in human or rat genomes (Zhang et al, 2008). A series of sequence variants of the DSG4 gene have been reported to induce lanceolate hair in mice and rats (Meyer et al, 2004;Zhang et al, 2008).…”