Type 1 Diabetes Models
Type 1 diabetes results from autoimmune destruction of pancreatic beta cells. Mouse models address both the immune and beta cell components of disease.
- NOD background models: Spontaneous autoimmune diabetes with genetic modifications
- Immune gene knockouts: Deletions affecting T cell, B cell, or innate immune function
- Beta cell specific deletions: Study genes essential for cell survival under immune attack
- Antigen presentation models: Modifications affecting MHC or antigen processing
Type 2 Diabetes Models
Type 2 diabetes involves both peripheral insulin resistance and eventual beta cell failure. Mouse models address these interconnected pathologies.
- Liver specific knockouts: Study hepatic glucose production and insulin sensitivity
- Adipose specific knockouts: Investigate adipokine signaling and lipid storage
- Muscle specific knockouts: Analyze glucose uptake and insulin signaling
- Beta cell specific knockouts: Study insulin secretion and beta cell compensation
Tissue Specific Approaches
Conditional knockouts enable dissection of gene function in specific metabolic tissues. A single floxed allele can be crossed to multiple Cre drivers to study gene function across metabolic tissues.
| Cre Driver | Target Tissue | Metabolic Function |
|---|---|---|
| Albumin Cre | Hepatocytes | Gluconeogenesis, lipid metabolism |
| Adiponectin Cre | Adipocytes | Lipid storage, adipokine secretion |
| Insulin Cre / Pdx1 Cre | Beta cells | Insulin secretion, beta cell mass |
| MCK Cre / MyoD Cre | Skeletal muscle | Glucose uptake, insulin sensitivity |
| Nestin Cre | Hypothalamus | Central metabolic regulation |
| Villin Cre | Intestinal epithelium | Incretin signaling, nutrient absorption |
Strain Background Considerations
Strain background significantly impacts metabolic phenotypes. The Nnt mutation in C57BL/6J should be considered when studying beta cell function or insulin secretion.
| Strain | Characteristics | Considerations |
|---|---|---|
| C57BL/6J | Nnt mutation impairs insulin secretion; susceptible to diet induced obesity | Document Nnt status; consider for obesity studies |
| C57BL/6N | Intact Nnt; more robust insulin secretion | Preferred for beta cell function studies |
| NOD | Spontaneous autoimmune diabetes | Required background for T1D studies |
| BALB/c | Relatively resistant to diet induced obesity | Less commonly used for metabolic studies |
Metabolic Phenotyping
Glucose Homeostasis
- •Fasting and fed blood glucose
- •Glucose tolerance testing (GTT)
- •Insulin tolerance testing (ITT)
- •Hyperinsulinemic euglycemic clamp
Insulin & Beta Cell
- •Fasting and stimulated insulin levels
- •HOMA IR and HOMA B calculations
- •Islet isolation and perifusion
- •Beta cell mass quantification
Body Composition
- •Body weight and food intake
- •Body composition (MRI, DEXA)
- •Indirect calorimetry
- •Activity monitoring
Selected Publications in Diabetes Research
Models generated by ingenious targeting laboratory have supported diabetes research:
Nargis T, Muralidharan C, Enriquez JR, Wang JE, Kaylan K, Chakraborty A, Pratuangtham S, Figatner K, Nelson JB, May SC, Nadler JL, Boxer MB, Maloney, DJ, Tersey SA, Mirmira RG. (2024).
12-Lipoxygenase inhibition delays onset of autoimmune diabetes in human gene replacement mice ↗JCI Insight 24(9): e185299
Ghosh A, Chénier I, Leung YH, Oppong AK, Peyot, M-L, Madiraju SRM, Al-Khairi I, Abubaker J, Al-Mulla F, Prentki M, Abu-Farha M. (2024).
Adipocyte Angptl8 deletion improves glucose and energy metabolism and obesity associated inflammation in mice ↗iScience 12(27): 111292
What Researchers Say
“I've been working with iTL over the past 5 years in the production of 3 different genetically altered mice. Not only did iTL help in the design of the mice, but the entire process was transparent with the opportunity at any time along the way to discuss my questions or concerns with scientists who had significant insight into the process. The mice were delivered on time, as billed!”
— Raghu Mirmira, MD, PhD
University of Chicago
Start Your Diabetes Model Project
Our scientific consultants are ready to discuss your diabetes research requirements and recommend the optimal model design for your program. Initial consultation is provided at no charge and includes target analysis, tissue specific Cre recommendations, and timeline estimates.
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