Age-associated motor and visuo-spatial learning phenotype in Dyrk1A heterozygous mutant mice

Dual-specificity tyrosine-regulated kinase 1A (DYRK1A) is a candidate gene for the Down syndrome neurological defects and may be involved in the progression of Alzheimer's disease. Heterozygous mice for Dyrk1A (Dyrk1A+/-) exhibit decreased brain size, motor abnormalities and cognitive deficits in the adult. However, there is no information about the mutant phenotype in old ages. Here we analyze the impact of Dyrk1A dosage reduction on motor performance and hippocampal-dependent learning and memory in aged Dyrk1A+/- mice. Whereas motor tests showed marked alterations in traction ability, prehensile reflex and balance, heterozygous mice only present a slight impairment of visuo-spatial memory even though they show a robust decrease of CA1-CA3 and dentate gyrus cells.