Down syndrome (DS) results from one extra copy of human chromosome 21 and leads 
to several alterations including intellectual disabilities and locomotor 
defects. The transchromosomic Tc1 mouse model carrying an extra 
freely-segregating copy of human chromosome 21 was developed to better 
characterize the relation between genotype and phenotype in DS. The Tc1 mouse 
exhibits several locomotor and cognitive deficits related to DS. In this report 
we analyzed the contribution of the genetic dosage of 13 conserved mouse genes 
located between Abcg1 and U2af1, in the telomeric part of Hsa21. We used the 
Ms2Yah model carrying a deletion of the corresponding interval in the mouse 
genome to rescue gene dosage in the Tc1/Ms2Yah compound mice to determine how 
the different behavioral phenotypes are affected. We detected subtle changes 
with the Tc1/Ms2Yah mice performing better than the Tc1 individuals in the 
reversal paradigm of the Morris water maze. We also found that Tc1/Ms2Yah 
compound mutants performed better in the rotarod than the Tc1 mice. This data 
support the impact of genes from the Abcg1-U2af1 region as modifiers of 
Tc1-dependent memory and locomotor phenotypes. Our results emphasize the complex 
interactions between triplicated genes inducing DS features.