Open AccessPathogenic and Compensatory Mechanisms in Epidermis of Sphingomyelin Synthase 2-Deficient Mice
Author(s) -
Shota Sakaï,
Asami Makino,
Akihito Nishi,
Takeshi Ichikawa,
Tadashi Yamashita,
Makoto Taniguchi,
Yoshihiro Tokudome,
Yoshio Hirabayashi,
Masashi Akiyama,
Debra Crumrine,
Yoshikazu Uchida,
Peter M. Elias,
Takaaki Tsuchida,
Sumiko Hamanaka
Publication year - 2021
Publication title -
skin pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.703
H-Index - 74
eISSN - 1660-5535
pISSN - 1660-5527
DOI - 10.1159/000515608
Subject(s) - sphingomyelin , lamellar granule , stratum corneum , microbiology and biotechnology , ceramide , epidermis (zoology) , biology , hyperkeratosis , endocrinology , knockout mouse , medicine , sphingolipid , chemistry , apoptosis , biochemistry , receptor , cholesterol , anatomy , genetics , pulmonary surfactant
Sphingomyelin (SM) is a constituent of cellular membranes, while ceramides (Cer) produced from SM on plasma membranes serve as a lipid mediator that regulates cell proliferation, differentiation, and apoptosis. In the skin, SM also is a precursor of Cer, an important constituent of epidermal permeability barrier. We investigated the role of epidermal SM synthase (SMS)2, an isoform of SMS, which modulates SM and Cer levels on plasma membranes. Although SMS2-knockout (SMS2-KO) mice were not neonatal lethal, an ichthyotic phenotype with epidermal hyperplasia and hyperkeratosis was evident at birth, which persisted until 2 weeks of age. These mice showed abnormal lamellar body morphology and secretion, and abnormal extracellular lamellar membranes in the stratum corneum. These abnormalities were no longer evident by 4 weeks of age in SMS2-KO mice. Our study suggests that (1) exposure to a dry terrestrial environment initiates compensatory responses, thereby normalizing epidermal ichthyotic abnormalities and (2) that a nonlethal gene abnormality can cause an ichthyotic skin phenotype.