Minocycline treatment reverses ultrasonic vocalization production deficit in a mouse model of Fragile X Syndrome

Fragile X Syndrome (FXS) is the most common inherited form of intellectual disability, with behaviors characteristic of autism. Symptoms include abnormal social behavior, repetitive behavior, communication disorders, and seizures. Many symptoms of FXS have been replicated in the Fmr1 knockout (KO) mice. Whether Fmr1 KO mice exhibit vocal communication deficits is not known. By recording ultrasonic vocalizations (USV) produced by adult male mice during mating, we show that USV calling rate (number of calls/second) is reduced in Fmr1 KO mice compared to WT controls. The WT control and Fmr1 KO groups did not differ in other aspects of mating behavior such as time spent sniffing, mounting, rooting and without contact. Acoustic properties of calls such as mean frequency (in kHz), duration and dynamic range of frequencies were not different. This indicates a specific deficit in USV calling rate in Fmr1 KO mice. Previous studies have shown that treatment of Fmr1 KO mice with minocycline for 4 weeks from birth can alleviate some behavioral symptoms. Here we tested if minocycline also reversed vocalization deficits in these mice. Calling rate increased and was similar to WT controls in adult Fmr1 KO mice treated with minocycline for four weeks from birth (P0–P28). All acoustic properties measured were similar in treated and untreated WT control mice indicating minocycline effects were specific to vocalizations in the Fmr1 KO mice. These data suggest that mating-related USVs are robust and relevant biomarkers of FXS, and that minocycline treatment is a promising avenue for treatment of FXS symptoms.

► Fragile X Syndrome model mice (Fmr1 knockout) produce USVs at a significantly lower rate than wild-type control.
► Other aspects of mating behavior are similar between wild-type and knockout mice.
► Four weeks of minocycline treatment from birth reverses the vocalization deficit.