(Scanned from the Applicant's Description): The majority of persons with non-insulin-dependent diabetes mellitus (NIDDM) are obese. Nevertheless, although most obese people have insulin resistance, the great majority never develop NIDDM. There are essentially no biochemical clues that allow us to predict which obese individuals will develop diabetes, much less why they develop diabetes. In addition, there is limited mechanistic information to help us understand why obesity is so intimately related to diabetes. The objective of this project is to identify genes that link obesity and diabetes in mice. We have mapped two gene loci that determine whether or not an obese mouse will develop Type 2 diabetes. We have also mapped two loci that strongly affect body weight in a population of obese hyperphagic mice.
The aims of this project are to: 1) Create interval-specific congenic strains for each mapped locus. 2) Refine the obesity and diabetes phenotypes. 3) Use a positional candidate strategy to identify the genes responsible for the mapped traits. Identification of obesity and diabetes susceptibility genes will provide clues to novel pathways and biochemical mechanisms underlying complex disease problems.
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| Attie, Alan D; Churchill, Gary A; Nadeau, Joseph H (2017) How mice are indispensable for understanding obesity and diabetes genetics. Curr Opin Endocrinol Diabetes Obes 24:83-91 |
| Gu, Tongjun; Gatti, Daniel M; Srivastava, Anuj et al. (2016) Genetic Architectures of Quantitative Variation in RNA Editing Pathways. Genetics 202:787-98 |
| Shortreed, Michael R; Wenger, Craig D; Frey, Brian L et al. (2015) Global Identification of Protein Post-translational Modifications in a Single-Pass Database Search. J Proteome Res 14:4714-20 |
| Bhatnagar, Sushant; Soni, Mufaddal S; Wrighton, Lindsay S et al. (2014) Phosphorylation and degradation of tomosyn-2 de-represses insulin secretion. J Biol Chem 289:25276-86 |
| Ulbrich, Arne; Merrill, Anna E; Hebert, Alexander S et al. (2014) Neutron-encoded protein quantification by peptide carbamylation. J Am Soc Mass Spectrom 25:6-9 |
| Munger, Steven C; Raghupathy, Narayanan; Choi, Kwangbom et al. (2014) RNA-Seq alignment to individualized genomes improves transcript abundance estimates in multiparent populations. Genetics 198:59-73 |
| Kebede, Melkam A; Attie, Alan D (2014) Insights into obesity and diabetes at the intersection of mouse and human genetics. Trends Endocrinol Metab 25:493-501 |
| Johnson, Lisa M; Barrick, Stacey; Hager, Marlies V et al. (2014) A potent ?/?-peptide analogue of GLP-1 with prolonged action in vivo. J Am Chem Soc 136:12848-51 |
| Neto, Elias Chaibub; Broman, Aimee T; Keller, Mark P et al. (2013) Modeling causality for pairs of phenotypes in system genetics. Genetics 193:1003-13 |
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