ArticleGenetics2014
Identification of a novel gene for diabetic traits in rats, mice, and humans.
Article in Genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
- Identification of novel candidate neural genes for diet-induced obesity in outbred heterogeneous stock rats.Research square · 2026Article
- Lysosomal dysfunction in diabetes and diabetic complications.Frontiers in endocrinology · 2026Review
- ZBiotics ameliorates T2DM-induced histopathological damage in liver, kidney and adipose tissues by modulating the NOD-like receptor signaling in Wistar rats.Diabetology & metabolic syndrome · 2025Article
- Autophagy-lysosome pathway in insulin & glucagon homeostasis.Frontiers in endocrinology · 2025Review
- The Power of the Heterogeneous Stock Rat Founder Strains in Modeling Metabolic Disease.Endocrinology · 2023Article
- Genetic background in the rat affects endocrine and metabolic outcomes of bisphenol F exposure.Toxicological sciences : an official journal of the Society of Toxicology · 2023Article
- NAADP-Mediated CaHandbook of experimental pharmacology · 2023Article
- Transcriptome-wide analyses of adipose tissue in outbred rats reveal genetic regulatory mechanisms relevant for human obesity.Physiological genomics · 2022Article
- Multi-Omic Approaches to Identify Genetic Factors in Metabolic Syndrome.Comprehensive Physiology · 2021Article
- Alternative exon splicing and differential expression in pancreatic islets reveals candidate genes and pathways implicated in early diabetes development.Mammalian genome : official journal of the International Mammalian Genome Society · 2021Article
- Bisphenol F Exposure in Adolescent Heterogeneous Stock Rats Affects Growth and Adiposity.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Early life stress induces hyperactivity but not increased anxiety-like behavior or ethanol drinking in outbred heterogeneous stock rats.Alcohol (Fayetteville, N.Y.) · 2021Article
- Sept8/SEPTIN8 involvement in cellular structure and kidney damage is identified by genetic mapping and a novel human tubule hypoxic model.Scientific reports · 2021Article
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
- Using Heterogeneous Stocks for Fine-Mapping Genetically Complex Traits.Methods in molecular biology (Clifton, N.J.) · 2019Review
- Two Novel Candidate Genes for Insulin Secretion Identified by Comparative Genomics of Multiple Backcross Mouse Populations.Genetics · 2018Article
- Two-pore channels and disease.Biochimica et biophysica acta. Molecular cell research · 2018Review
- A collective diabetes cross in combination with a computational framework to dissect the genetics of human obesity and Type 2 diabetes.Human molecular genetics · 2018Article
- Tpcn2 knockout mice have improved insulin sensitivity and are protected against high-fat diet-induced weight gain.Physiological genomics · 2018Article
- Review
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Authors and funding
20 authors at 3 institutions in 2 countries.
Funding
Abstract
The genetic basis of type 2 diabetes remains incompletely defined despite the use of multiple genetic strategies. Multiparental populations such as heterogeneous stocks (HS) facilitate gene discovery by allowing fine mapping to only a few megabases, significantly decreasing the number of potential candidate genes compared to traditional mapping strategies. In the present work, we employed expression and sequence analysis in HS rats (Rattus norvegicus) to identify Tpcn2 as a likely causal gene underlying a 3.1-Mb locus for glucose and insulin levels. Global gene expression analysis on liver identified Tpcn2 as the only gene in the region that is differentially expressed between HS rats with glucose intolerance and those with normal glucose regulation. Tpcn2 also maps as a cis-regulating expression QTL and is negatively correlated with fasting glucose levels. We used founder sequence to identify variants within this region and assessed association between 18 variants and diabetic traits by conducting a mixed-model analysis, accounting for the complex family structure of the HS. We found that two variants were significantly associated with fasting glucose levels, including a nonsynonymous coding variant within Tpcn2. Studies in Tpcn2 knockout mice demonstrated a significant decrease in fasting glucose levels and insulin response to a glucose challenge relative to those in wild-type mice. Finally, we identified variants within Tpcn2 that are associated with fasting insulin in humans. These studies indicate that Tpcn2 is a likely causal gene that may play a role in human diabetes and demonstrate the utility of multiparental populations for positionally cloning genes within complex loci.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.