Essential role of the nucleotide-sugar transporter Slc35d1 in intestinal homeostasis

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670170
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Kobe Pharmaceutical University
• Principal Investigator: SHUICHI Hiraoka 神戸薬科大学, 薬学部, 研究員 (20291156)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 糖ヌクレオチド輸送体 / 腸管機能 / ホメオスタシス / コンドロイチン硫酸

Outline of Final Research Achievements

The nucleotide-sugar transporter Slc35d1 transports the substrates for chondroitin sulfate (CS) and heparan sulfate from cytosol into lumens of Golgi apparatus and ER. To investigate in vivo role of the Slc35d1, we generated Slc35d1flox-Rosa CreERT mice (Slc35d1-iKO mouse), of which Slc35d1 gene could be artificially disrupted by the administration of tamoxifen (TXF). The Slc35d1-iKO mouse was dead within 10 days by the TXF administration, suffering from diarrhea. We observed the intestinal villous atrophy and 30% reduction of CS prior to morphological affection of villi. Based on these observations, we concluded that the Slc35d1 is required for intestinal homeostasis. It is likely that reduction of the CS in the Slc35d1-iKO mouse induced villous atrophy leading to lethal malnutrition.

Free Research Field

生化学、遺伝学