Motor deficits on a ladder rung task in male and female adolescent and adult CGG knock-in mice

The fragile X premutation is a tandem CGG trinucleotide repeat expansion on the FMR1 gene between 55 and 200 repeats in length. A CGG knock-in (CGG KI) mouse with CGG trinucleotide repeat lengths between 70 and 350 has been developed and used to model the histopathology and cognitive deficits reported in carriers of the fragile X premutation. Previous studies have shown that CGG KI mice show progressive deficits in processing spatial and temporal information. To characterize the motor deficits associated with the fragile X premutation, male and female CGG KI mice ranging from 2 to 16 months of age with trinucleotide repeats ranging from 72 to 240 CGG in length were tested for their ability to perform a skilled ladder rung walking test. The results demonstrate that both male and female CGG KI mice showed a greater number of foot slips as a function of increased CGG repeat length, independent of the age of the animal or general activity level.

► CGG KI mice show early onset motor deficits, modeling gait ataxia seen in FXTAS. ► Ladder rung task is a sensitive motor task to quantify motor deficits in mouse models. ► CGG repeat length on Fmr1 gene is associated with lager motor deficits in CGG KI mice.