title: Analysis of development of lesions in mice with serine palmitoyltransferase (SPT) deficiency -Sptlc2 conditional knockout mice-.
abstract: Serine palmitoyltransferase (SPT) is the enzyme which catalyzes the first step of the biosynthesis of sphingolipids. However, the precise roles of SPT in vivo are not well understood, since complete knockout (KO) of genes which compose SPT results in a fetal lethal phenotype. A conditional KO (cKO) mouse of SPT long chain base 2 (Sptlc2) was therefore developed, and the effects of Sptlc2 deficiency were examined. Single cell necrosis in the epithelia of the crypts of the small and large intestines was observed as early as 24 h after induction of knockout. At 48 h after induction, decreases in spleen and thymus weights and decreases in numbers of reticulocytes and lymphocytes were observed in cKO mice, and single cell necrosis in the intestine became prominent. At 72 h after induction, decreases in body weight, spleen and thymus weights, and numbers of reticulocytes and lymphocytes became obvious in cKO mice. Histologically, atrophy of gastrointestinal mucosa and lymphoid necrosis as well as depletion of lymphoid and hematopoietic tissues were observed. These findings suggest that SPT plays important roles in the maintenance of the gastrointestinal mucosa, especially in the proliferation of the mucosal epithelial cells, and that deficiency of Sptlc2 induces necrotic lesions in gastrointestinal cells followed by atrophic change of the tissue in short term.
authors.affiliation: Safety Assessment, Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Tsukuba, Ibaraki, Japan.
authors.forename: Etsuko
authors.initials: E
authors.lastname: Ohta
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohira
authors.forename: Kenta
authors.initials: K
authors.lastname: Matsue
authors.forename: Yuika
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Kenji
authors.initials: K
authors.lastname: Fujii
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohwaki
authors.forename: Sou
authors.initials: S
authors.lastname: Osuka
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hirabayashi
authors.forename: Minoru
authors.initials: M
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D001284:Atrophy; D002452:Cell Count; D049109:Cell Proliferation; D002678:Chimera; D005260:Female; D006410:Hematopoiesis; D007413:Intestinal Mucosa / Q000473:pathology*; D007420:Intestine, Large / Q000473:pathology*; D007421:Intestine, Small / Q000473:pathology; D008214:Lymphocytes / Q000473:pathology; D008221:Lymphoid Tissue / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D009929:Organ Size / Q000235:genetics; D012156:Reticulocytes / Q000473:pathology; D051102:Serine C-Palmitoyltransferase / Q000172:deficiency / Q000502:physiology*; D013107:Sphingolipids / Q000096:biosynthesis / Q000235:genetics; D013154:Spleen / Q000473:pathology; D013629:Tamoxifen / Q000494:pharmacology; D013950:Thymus Gland / Q000473:pathology
chemical_list: D013107:Sphingolipids; D013629:Tamoxifen; D051102:Serine C-Palmitoyltransferase; C495090:Sptlc2 protein, mouse