-実験動物開発室-

B6;129(FVB)-Sptlc2<tm1.1Yhir> (RBRC09802)

Courtesy of Yoshio Hirabayashi, Ph.D.

Progressive and selective Purkinje cell degeneration in conditional Sptlc2 knockout mouse. Sagittal sections were immunostained with anti-calbindin.

Sphingolipids are a class of lipids containing a backbone of hydrophobic chain of ceramide. They are ubiquitously distributed in biological membranes and play important roles in signal transmission, vesicular transport, cell homeostasis, and cell-cell interaction. Sphingolipids are abundant in the CNS tissues and the lipid synthesis is essential for dendritic development and survival of cerebellar Purkinje neurons [1]. Serine palmitoyltransferase (SPT, EC 2.3.1.50) is the enzyme which catalyzes the first step of the sphingolipid biosynthesis. SPT consists mainly of long chain base subunit 1 (SPTLC1) and 2/3. SPTLC2 encoded by the Sptlc2 is essential component for activities. In humans, mutations in the SPTLC2 cause hereditary sensory and autonomic neuropathy type I [2]. The complete knockout (KO) of Sptlc2 results in a fetal lethal phenotype. Thus, the Sptlc2 floxed mice were developed to study physiological roles of sphingolipid synthesis [3]. Figure shows selective cell death of cerebellar Purkinje neurons in the specific KO mouse (Osuka et al., unpublished results). Recent studies by Summers group demonstrated that sphingolipid plays a critical role in adipocyte physiology [4]. Thus, the cKO mice are useful tools to elucidate in vivo functions of sphingolipid synthesis in central and peripheral tissues.