Disease relevance of Gsdm3

• The adult Bsk mouse manifests hair loss and corneal opacity [1].

High impact information on Gsdm3

• The gene underlying the phenotype of both finnegan and defolliculated has been mapped to chromosome 11 and here we show that both mice harbor mutations in gasdermin 3 (Gsdm3), a gene of unknown function [2].
• Recently a similar mutant, finnegan (Fgn), with an identical phenotype was discovered during a phenotypic screen for mutations induced by chemical mutagenesis [2].
• Mutations in gasdermin 3 cause aberrant differentiation of the hair follicle and sebaceous gland [2].
• We provide evidence for a murine-specific gene cluster consisting of Gsdm and two closely related genes which we designate as Gsdm2 and Gsdm3 [3].
• We infer a role of Gsdm3 during the catagen to telogen transition at the end of hair follicle morphogenesis and the formation of hair follicle-associated sebaceous glands [3].

Biological context of Gsdm3

• These findings suggest that Bsk/Iyk might play a role in inhibiting cell proliferation, transducing cytokine-induced cytotoxicity and regulating hormone production of endocrine pancreatic cells [4].
• The Bsk/IykY497/504F cells displayed a decreased cell growth rate, parallelled by an augmentation of the fraction of cells in G1-phase [5].

Anatomical context of Gsdm3

• Reduced Coat 2 (Rco2) is an ENU-induced mutation affecting hair follicle morphogenesis by an abnormal and protracted catagen [3].
• Expression of an acidic 50 kD keratin, recognized by monoclonal antibody AK 2, was up-regulated in the injured corneas of normal mice as well as Bsk corneas [1].
• Wild-type Bsk/Iyk is mainly localized at the plasma membrane whereas mutant Bsk/Iyk can enter the nucleus [4].
• The Y497F Bsk/Iyk mutant not only increased the relative amount of p57 Bsk/Iyk but also transferred this isoform to the nuclear subcellular fraction [5].
• The Src-like tyrosine kinase mouse Gtk (previously named Bsk/Iyk) is expressed in islet cells, and was found to inhibit cell proliferation [6].

Associations of Gsdm3 with chemical compounds

• Role of the Bsk/Iyk non-receptor tyrosine kinase for the control of growth and hormone production in RINm5F cells [4].

Other interactions of Gsdm3

• These data ruled out the hypothesis that Bsk phenotype results from a recombination event between K12 and mHa 1, 2, 3 and 4 [1].

Analytical, diagnostic and therapeutic context of Gsdm3

• METHODS: The Bsk phenotype was examined by histochemical analysis, using light and electron microscopy [1].
• RESULTS: Northern hybridization, RT-PCR and Western blot analysis revealed that mHa 1, 2, 3 and 4 keratins are expressed in the skin, but not in cornea, whereas the expression of K12 is limited to the corneas of the Bsk mice [1].

References