Glucose tolerance female-specific QTL mapped in collaborative cross mice

Area of Science:

• Genetics
• Metabolic Diseases
• Animal Models

Background:

• Type-2 diabetes (T2D) is a complex metabolic disorder influenced by both environmental factors and host genetics.
• Understanding the genetic underpinnings of glucose tolerance is crucial for T2D prevention and treatment.

Purpose of the Study:

• To map quantitative trait loci (QTL) associated with glucose tolerance variations in genetically diverse mouse strains.
• To investigate potential sex-specific genetic influences on glucose tolerance.

Main Methods:

• Utilized 501 mice from 58 Collaborative Cross (CC) lines fed a high-fat diet for 12 weeks.
• Performed intraperitoneal glucose tolerance tests (IPGTT) and measured Area Under the Curve (AUC0-180) for QTL analysis.
• Calculated heritability and coefficient of genetic variance (CVg) for glucose tolerance.

Main Results:

• Significant variations in glucose tolerance (AUC0-180) were observed between CC lines and sexes.
• A significant female-sex-dependent QTL on Chromosome 8 was identified, associated with IPGTT AUC0-180.
• The QTL region contained genes related to body weight, immune function, and glucose homeostasis (Mboat4, Leprotl1).

Conclusions:

• Genetic factors play a significant role in controlling glucose tolerance, with notable differences between sexes.
• The identified female-specific QTL underscores the importance of sex-specific approaches in T2D research.
• Further investigation into sex-specific genetic factors is essential for developing targeted T2D prevention and therapies.