Yesterday's post on mice mating songs left with a final question: Do FoxP2 knockout mice sing?
Thanks to a kind reader, I have a probable answer: no.
Although nobody has looked specifically at ultrasonic vocalizations in response to mating (since they didn't know about the singing before), they have studied ultrasonic vocalizations in pups when they are separated from their mothers. This paper by Weiguo Shu and colleagues (2005)</a> studied such vocalizations in both heterozygous and homozygous knockouts.
Because FOXP2 has been directly implicated in speech and articulation, we examined the incidence of ultrasonic vocalizations in pups removed from their mothers. Ultrasonic calls are important for motherinfant social interaction (16) and represent important markers for neurobehavioral development (17). At postnatal day 6, the incidence of vocalization over time was dramatically reduced in both heterozygous and knockout animals as measured by automated vocalization monitoring (Fig. 4a). Repeated measures analysis demonstrated differences in mean number of vocalizations (P < 0.0005 for wild-type versus knockout and P = 0.008 for wild-type versus heterozygotes).
Based on these results, we performed a spectrographic analysis of an independent group of animals at postnatal day 10 (e.g., Fig. 4b). There was a profound decrease in the number of ultrasonic vocalizations in heterozygous and homozygous knockout animals (Fig. 4c). The duration, peak frequency, and bandwidth of these vocalizations in the heterozygous animals were indistinguishable from wild-type animals (data not shown). In the course of these analyses, we also examined broad-spectrum clicks made by the mice. These clicks are of unknown function (18), and the information content of them has not been studied. Heterozygous and homozygous knockout animals were able to produce clicks, but the homozygous knockout animals produced clicks at a reduced incidence (Fig. 4d). The duration, peak frequency, and bandwidth of these vocalizations in the heterozygous and homozygous knockout animals were indistinguishable from wild-type animals (emphasis added).
Homozygote knockouts died prematurely, by 21 days after birth. Heterozygotes lived, but exhibited developmental delays.
The paper included histological study of the brains of the knockout mice, with this interesting finding:
No overt abnormalities were detected in the histologic appearance of the cerebral hemispheres and the subcortical structures, including the midbrain and pons. However, the knockout mice demonstrated the presence of a 3- to 4-cell thick external granular layer (EGL) at postnatal days 1517, well after the normal resolution of the EGL (Fig. 3 af). The heterozygous animals retained a one-cell-thick EGL at this age, whereas the wild-type mice were free of this early developmental feature. By adulthood, the EGL was absent in heterozygous animals (data not shown).
Granule cell progenitors in the EGL migrate to their final position in the granule cell layer along the radial fibers of the Bergmann glia (14). To determine whether the persistence of an EGL in the knockout animal might be at least, in part, explained by a failure of radial glial development, we stained radial glial fibers in cerebellar sections from postnatal day 17 animals with GFAP immunostaining (Fig. 3 jl). Radial glial fibers were visible in all genotypes. However, in contrast to the regularly aligned radial glial fibers in the wild-type animals, fibers in the heterozygous animals were in some areas thinner and less well aligned. In the knockout animals, there were often gaps in the radial glial network as well as areas where fibers appeared to be clumped into aggregates.
It's interesting to me that neural cell migration appears to be (at least one) important effect of the gene. This is the developmental step that forms the circuits in the brain.
Shu W, Cho JY, Jiang Y, Zhang M, Weisz D, Elder GA, Schmeidler J, De Gasperi R, Sosa MA, Rabidou D, Santucci AC, Perl D, Morrisey E, Buxbaum JD. 2005. Altered ultrasonic vocalization in mice with a disruption in the Foxp2 gene. Proc Natl Acad Sci U S A 102:9643-9648. Full text (free)