Abstract
Heterozygous mutations of the human FOXP2 gene are implicated in a severe speech and language disorder. Aetiological mutations of murine Foxp2 yield abnormal synaptic plasticity and impaired motor-skill learning in mutant mice, while knockdown of the avian orthologue in songbirds interferes with auditory-guided vocal learning. Here, we investigate influences of two distinct Foxp2 point mutations on vocalizations of 4-day-old mouse pups (Mus musculus). The R552H missense mutation is identical to that causing speech and language deficits in a large well-studied human family, while the S321X nonsense mutation represents a null allele that does not produce Foxp2 protein. We ask whether vocalizations, based solely on innate mechanisms of production, are affected by these alternative Foxp2 mutations. Sound recordings were taken in two different situations: isolation and distress, eliciting a range of call types, including broadband vocalizations of varying noise content, ultrasonic whistles and clicks. Sound production rates and several acoustic parameters showed that, despite absence of functional Foxp2, homozygous mutants could vocalize all types of sounds in a normal temporal pattern, but only at comparably low intensities. We suggest that altered vocal output of these homozygotes may be secondary to developmental delays and somatic weakness. Heterozygous mutants did not differ from wild-types in any of the measures that we studied (R552H) or in only a few (S321X), which were in the range of differences routinely observed for different mouse strains. Thus, Foxp2 is not essential for the innate production of emotional vocalizations with largely normal acoustic properties by mouse pups.
Highlights
Heterozygous mutations of human FOXP2 cause severe speech and language disorders (Lai et al 2001; MacDermot et al 2005) involving deficits in rapid coordinated orofacial movements and impaired expression and reception of language (Watkins et al 2002)
There was evidence of reduced body weight compared with wild-types and heterozygotes already at postnatal day 4 (ANOVA on ranks, P < 0.01 for the R552H line and P < 0.001 or P < 0.05 for the S321X line; Fig. 1)
There were significantly lower numbers of ultrasounds in response to isolation (USIs) from homozygotes of both mouse lines compared with the respective heterozygotes and wild-types, while significantly more S321X homozygotes produced USIs compared with R552H homozygotes
Summary
Heterozygous mutations of human FOXP2 cause severe speech and language disorders (Lai et al 2001; MacDermot et al 2005) involving deficits in rapid coordinated orofacial movements and impaired expression and reception of language (Watkins et al 2002). Heterozygous mice with disrupted Foxp show abnormal synaptic plasticity in relevant circuits and impaired motor-skill learning (Groszer et al 2008). Whether and how their vocalizations are changed remains to be clarified in view of differences in data (Fujita et al 2008; Groszer et al 2008; Shu et al 2005). Compared with data on humans and songbirds, we separate possible impacts of Foxp mutations on innate motor coordination from effects on motor-skill learning
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