Federal Grant Award Summary

Indiana University Indianapolis received a $692,850 Project Grant award from the National Institutes of Health (NIH) Office of the Director under the Trans-NIH Research Support program (CFDA 93.310), effective July 1, 2026, through March 31, 2030. The award funds the development of novel Down syndrome mouse models designed to systematically characterize sex-specific phenotypes and their developmental origins. Specifically, the research creates new mouse models by crossing DP16 mice (which carry triplicated genes mimicking trisomy 21) with Four Core Genotype (FCG) mice, which allows researchers to separately isolate the contributions of gonadal sex and sex chromosomal complement to disease manifestation. This approach addresses a critical gap in Down syndrome preclinical research, where historical male-biased models and small sample sizes have obscured sex-specific differences in disease presentation.

The project will conduct systematic longitudinal analysis of hormone levels and developmental phenotypes across eight distinct mouse groups to delineate how sex-specific traits in Down syndrome emerge before and after puberty. By determining whether sex differences originate from gonadal secretions or sex chromosome gene expression, the research aims to improve the translational validity of Down syndrome mouse models and potentially inform sex-differentiated treatment approaches for individuals with Down syndrome. This work represents the first comprehensive effort to characterize the biological sources of sexual dimorphisms in Down syndrome phenotypes using a controlled genetic model.