Spontaneous nonsense mutation in the tuftelin 1 gene is associated with abnormal hair appearance and amelioration of glucose and lipid metabolism in the rat
Language English Country United States Media print-electronic
Document type Journal Article
Grant support
LX22NPO5104
European Union/Ministry of Education of the Czech Republic
LM2023067
Ministry of Education of the Czech Republic
21-18993S
Czech Science Foundation
- Keywords
- Tuft1, hepatic proteome, lipid and glucose metabolism, rat, spontaneous nonsense mutation, tuftelin 1 gene,
- MeSH
- Glucose * metabolism MeSH
- Insulin metabolism MeSH
- Rats MeSH
- Lipid Metabolism genetics MeSH
- Codon, Nonsense * genetics MeSH
- Rats, Inbred BN MeSH
- Rats, Inbred SHR MeSH
- Proteome metabolism MeSH
- Inflammation MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Glucose * MeSH
- Insulin MeSH
- Codon, Nonsense * MeSH
- Proteome MeSH
- tuftelin MeSH Browser
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.NEW & NOTEWORTHY A new spontaneous mutation, abnormal hair appearance in the rat, has been identified as a nonfunctional tuftelin 1 (Tuft1) gene. The pleiotropic effects of this mutation regulate glucose and lipid metabolism. Analysis of the liver proteome revealed possible molecular mechanisms for the metabolic effects of the Tuft1 gene.
Department of Pathology 3rd Faculty of Medicine Charles University Prague Czech Republic
Institute of Physiology Czech Academy of Sciences Prague Czech Republic
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