Abstract
Fragile X syndrome (FXS) is a well-recognized form of inherited mental retardation, caused by a mutation in the fragile X mental retardation 1 (Fmr1) gene. The gene is located on the long arm of the X chromosome and encodes fragile X mental retardation protein (FMRP). Absence of FMRP in fragile X patients as well as in Fmr1 knockout (KO) mice results, among other changes, in abnormal dendritic spine formation and altered synaptic plasticity in the neocortex and hippocampus. Clinical features of FXS include cognitive impairment, anxiety, abnormal social interaction, mental retardation, motor coordination and speech articulation deficits. Mouse pups generate ultrasonic vocalizations (USVs) when isolated from their mothers. Whether those social ultrasonic vocalizations are deficient in mouse models of FXS is unknown. Here we compared isolation-induced USVs generated by pups of Fmr1-KO mice with those of their wild type (WT) littermates. Though the total number of calls was not significantly different between genotypes, a detailed analysis of 10 different categories of calls revealed that loss of Fmr1 expression in mice causes limited and call-type specific deficits in ultrasonic vocalization: the carrier frequency of flat calls was higher, the percentage of downward calls was lower and that the frequency range of complex calls was wider in Fmr1-KO mice compared to their WT littermates.
Highlights
Fragile X syndrome affects approximately 1/4000 males
A total of 1399 calls from wild type (WT) mice (N = 10) and 1543 calls from fragile X mental retardation 1 (Fmr1) KO mice (N = 10) were recorded and classified. Based on this classification we identified three deficits in ultrasonic vocalizations (USVs) calls in pups of Fmr1 KO mice
We report that loss of Fmr1 expression in a mouse model of fragile X syndrome does not cause a change in the number of isolation induced USVs generated by 8 day pups
Summary
Fragile X syndrome affects approximately 1/4000 males. Most male fragile X patients have moderate to severe delays in the onset of speech and language. Articulation deficits are found in male and female FXS patients, [2,3]. Speech articulation problems impact their social interactions because the generation of socially meaningful spoken language includes the ability to modulate tone, volume and prosody (ups and downs of the voice). 30% of male FXS patients have autism, as determined by the standardized criteria of the Autism Diagnostic Observation Scale (ADOS) and the Autism Diagnostic Interview (ADI-R) [5,6,7]. Among the remaining FXS patients who do not meet the criteria for an autism spectrum disorder (ASD), the majority have one or more autistic features [5]
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