The main purpose of this combined core is to provide a comprehensive service using state-of-the-art molecular and genetic methods to generate a variety of sophisticated knock-in, knock-out and transgenic mice for DRC investigators in their type 1 and type 2 diabetes research. We have successfully generated many lines of knock-in, knock-out and transgenic mice related to diabetes studies. It is noteworthy three ofthe highlights among all the animals generated during the previous funding cycle. Firstly, humanized mice, which carry 5 human genes by sequential re-targeting the same ES cells. The engraftment of human fetal liver-derived CD34+ hematopoietic stem cells can reach nearly 100% and last up to 9 months in this humanized mouse. Secondly, lines of innate immunity deficient NOD mice for the studies of type 1 diabetes, especially in association with exogenous and endogenous environmental factors. Using MyD88 deficient NOD mice generated by the core, DRC investigators demonstrated the importance of commensal flora in type 1 diabetes development and gut flora is an environmental modifier that influence diabetes onset Thirdly, lines of inflammsome deficient B6 mice for the studies of metabolic syndrome and type 2 diabetes. DRC investigators found that inflammasomes NLRP3 and NLRP6 negatively regulate NAFLD progression and obesity via modulation ofthe gut flora. This combined core consists of three subcores - Molecular, Gene targeting and Mouse breeding (MGM) components. Each subcore has its distinct function while all is interconnected. We will continue to provide our outstanding service for Yale DRC community. Moleculai: subcore will increase the use of improved high efficiency BAC mutagenesis to facilitate the generation of customized constructs for both type 1 and type 2 diabetes studies. Together with Molecular subcore. Gene targeting subcore will extend the humanized mouse model systems to include diabetes-related genes in order to evaluate preclinical testing of new therapies and/or vaccines, by our DRC investigators, for treatment and prevention type 1 diabetes. Mouse breeding subcore will backcross the improved humanized mouse lines to NOD background and several lines of infammasome deficient mice to pure NOD background forthe studies of type 1 diabetes.

Public Health Relevance

The creation of novel mouse models through genetic engineering provides new insights into the mechanisms responsible for the development of human diabetes and a means of testing novel therapies for the disease.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Center Core Grants (P30)
Project #
Application #
Study Section
Special Emphasis Panel (ZDK1-GRB-S (O2))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Yale University
New Haven
United States
Zip Code
Roshandel, Delnaz; Klein, Ronald; Klein, Barbara E K et al. (2016) New Locus for Skin Intrinsic Fluorescence in Type 1 Diabetes Also Associated With Blood and Skin Glycated Proteins. Diabetes 65:2060-71
Huang, Fang; Sirinakis, George; Allgeyer, Edward S et al. (2016) Ultra-High Resolution 3D Imaging of Whole Cells. Cell 166:1028-40
Jeong, Jaekwang; VanHouten, Joshua N; Dann, Pamela et al. (2016) PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer. Proc Natl Acad Sci U S A 113:E282-90
Tai, Ningwen; Peng, Jian; Liu, Fuqiang et al. (2016) Microbial antigen mimics activate diabetogenic CD8 T cells in NOD mice. J Exp Med 213:2129-46
Kumamoto, Yosuke; Camporez, Joao Paulo G; Jurczak, Michael J et al. (2016) CD301b(+) Mononuclear Phagocytes Maintain Positive Energy Balance through Secretion of Resistin-like Molecule Alpha. Immunity 45:583-96
Nagarajan, Arvindhan; Petersen, Max C; Nasiri, Ali R et al. (2016) MARCH1 regulates insulin sensitivity by controlling cell surface insulin receptor levels. Nat Commun 7:12639
Costa, Diana K; Huckestein, Brydie R; Edmunds, Lia R et al. (2016) Reduced intestinal lipid absorption and body weight-independent improvements in insulin sensitivity in high-fat diet-fed Park2 knockout mice. Am J Physiol Endocrinol Metab 311:E105-16
Jaser, Sarah S; Patel, Niral; Xu, Meng et al. (2016) Stress and Coping Predicts Adjustment and Glycemic Control in Adolescents with Type 1 Diabetes. Ann Behav Med :
Saggar, Manish; Tsalikian, Eva; Mauras, Nelly et al. (2016) Compensatory Hyper-Connectivity in Developing Brains of Young Children with Type 1 Diabetes. Diabetes :
Sun, Xue; Veldhuizen, Maria G; Babbs, Amanda E et al. (2016) Perceptual and Brain Response to Odors Is Associated with Body Mass Index and Postprandial Total Ghrelin Reactivity to a Meal. Chem Senses 41:233-48

Showing the most recent 10 out of 530 publications