INVESTIGATING THE ROLE OF TWO NEW GENES POTENTIALLY INVOLVED IN LIPID METABOLISM

The purpose of this project is to observe the function of SPTY2D1 (suppressor of TY, domain containing 1) and TM6SF2 (transmembrane 6 superfamily member 2) in mice. Genetic studies in patients have identified isoforms of these genes associated with abnormal lipid and other metabolic profiles. As the detailed functions of these proteins are still unknown, we are studying the effects of the downregulation of these genes in mouse models. The mouse strains we are studying were created by inserting a new piece of DNA in the genome to disrupt the normal function of each gene. The resulting effect is to inactivate the corresponding gene interrupting the normal production of the protein. These two strains of mice are bred. To identify the mice with the proper genotype, ear piece biopsies are collected and genomic DNA is extracted. The identification of the mutation is done by PCR with specific primers amplifying the region of the genes and analyzed by estimating their sizes in an agarose gel after electrophoresis. The initial phenotypic characterization of these mice is to determine if mice unable to express the protein, called knock-out (KO), have a different body weight and growth (snout to anus length) compared to unmodified, wild type (WT), animals. While both strain KO animals have a decrease in the body weight compared to matched WT controls, only SPTY2D1-KO have a decreased body mass index (BMI). TM6SF2-KO and control WT have similar BMI due to a reduction in length responsible for the lesser weight measured.