Spontaneous nonsense mutation in the tuftelin 1 gene is associated with abnormal hair appearance and amelioration of glucose and lipid metabolism in the rat

0583232 - FGÚ 2025 RIV US eng J - Journal Article
Šilhavý, Jan - Mlejnek, Petr - Šimáková, Miroslava - Liška, František - Malínská, H. - Marková, I. - Hüttl, M. - Miklánková, D. - Mušálková, D. - Stránecký, V. - Kmoch, S. - Sticová, E. - Vrbacký, Marek - Mráček, Tomáš - Pravenec, Michal
Spontaneous nonsense mutation in the tuftelin 1 gene is associated with abnormal hair appearance and amelioration of glucose and lipid metabolism in the rat.
Physiological Genomics. Roč. 56, č. 1 (2024), s. 65-73. ISSN 1094-8341. E-ISSN 1531-2267
R&D Projects: GA MŠMT(CZ) LX22NPO5104; GA MŠMT(CZ) LUAUS23095; GA ČR(CZ) GA21-18993S
Research Infrastructure: NCMG III - 90267
Institutional support: RVO:67985823
Keywords : hepatic proteome * lipid and glucose metabolism * rat * spontaneous nonsense mutation * tuftelin 1 gene * Tuft1
OECD category: Cardiac and Cardiovascular systems
Impact factor: 4.6, year: 2022
https://doi.org/10.1152/physiolgenomics.00084.2023

Recently, we have identified a recessive mutation, an abnormal coat appearance in the BXH6 strain, a member of the HXB/BXH set of recombinant inbred (RI) strains. The RI strains were derived from the spontaneously hypertensive rat (SHR) and Brown Norway rat (BN-Lx) progenitors. Whole genome sequencing of the mutant rats identified the 195875980 G/A mutation in the tuftelin 1 (Tuft1) gene on chromosome 2, which resulted in a premature stop codon. Compared with wild-type BXH6 rats, BXH6-Tuft1 mutant rats exhibited lower body weight due to reduced visceral fat and ectopic fat accumulation in the liver and heart. Reduced adiposity was associated with decreased serum glucose and insulin and increased insulin-stimulated glycogenesis in skeletal muscle. In addition, mutant rats had lower serum monocyte chemoattractant protein-1 and leptin levels, indicative of reduced inflammation. Analysis of the liver proteome identified differentially expressed proteins from fatty acid metabolism and β-oxidation, peroxisomes, carbohydrate metabolism, inflammation, and proteasome pathways. These results provide evidence for the important role of the Tuft1 gene in the regulation of lipid and glucose metabolism and suggest underlying molecular mechanisms.
Permanent Link: https://hdl.handle.net/11104/0351234