Summary
Developmental delays and intellectual disabilities are common co-occurring conditions in Down syndrome, which is associated with an extra copy of human chromosome 21, and our proposed research aims to identify new target genes with therapeutic potential for improving cognitive function and thus the quality of life in people afflicted with this chromosomal alteration. These genes will be identified through the use of phenotype-based tests in mouse models tailor-made to facilitate genetic dissection of Down syndrome, and these models will be developed with the aid of CRISPR genome engineering technology. We will also test whether the characteristic features of Down syndrome are impacted by the gene-dosage-independent effects of trisomy 21, such as through alterations in the nuclear architecture, which could help to transform the current paradigm of understanding for Down syndrome-associated cognitive deficits.