Institute of Neurobiology, University of Ulm, Ulm, Germany.
Genes Brain Behav. 2010 Jun 1;9(4):390-401. doi: 10.1111/j.1601-183X.2010.00570.x. Epub 2010 Jan 30.
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.
人类 FOXP2 基因的杂合突变与严重的言语和语言障碍有关。鼠类 Foxp2 的病因突变导致突变小鼠的突触可塑性异常和运动技能学习受损，而禽类同源物在鸣禽中的敲低则干扰了听觉引导的发声学习。在这里，我们研究了两种不同的 Foxp2 点突变对 4 天大的小鼠幼崽（Mus musculus）发声的影响。R552H 错义突变与导致一个大型经过充分研究的人类家族言语和语言缺陷的突变相同，而 S321X 无义突变代表一个不产生 Foxp2 蛋白的无效等位基因。我们询问这些替代 Foxp2 突变是否会影响仅基于产生的先天机制的发声。在两种不同的情况下进行了声音记录：隔离和痛苦，引发了一系列叫声类型，包括具有不同噪声含量的宽带发声、超声哨声和点击声。声音产生率和几个声学参数表明，尽管缺乏功能性 Foxp2，纯合突变体仍可以以正常的时间模式发出所有类型的声音，但强度仅相对较低。我们认为，这些纯合子发声输出的改变可能是由于发育延迟和躯体虚弱所致。杂合突变体在我们研究的任何指标上都与野生型没有差异（R552H），或者只有少数指标有差异（S321X），这与不同小鼠品系之间通常观察到的差异处于同一范围内。因此，Foxp2 对于具有基本正常声学特性的情绪发声的先天产生不是必需的。
