Editing FOXP2 (section)

=== Mice ===
In a mouse ''FOXP2'' [[gene knockout]]s, loss of both copies of the gene causes severe motor impairment related to cerebellar abnormalities and lack of [[ultrasound|ultrasonic]] [[Animal communication|vocalisations]] normally elicited when pups are removed from their mothers.<ref name="Shu_2005"/> These vocalizations have important communicative roles in mother–offspring interactions. Loss of one copy was associated with impairment of ultrasonic vocalisations and a modest developmental delay. Male mice on encountering female mice produce complex ultrasonic vocalisations that have characteristics of song.<ref name="Holy_2005">{{cite journal | vauthors = Holy TE, Guo Z | title = Ultrasonic songs of male mice | journal = PLOS Biology | volume = 3 | issue = 12 | pages = e386 | date = December 2005 | pmid = 16248680 | pmc = 1275525 | doi = 10.1371/journal.pbio.0030386 | doi-access = free }}</ref> Mice that have the R552H point mutation carried by the KE family show cerebellar reduction and abnormal [[synaptic plasticity]] in striatal and [[cerebellar]] circuits.<ref name="Groszer 2008"/>

Humanized FOXP2 mice display altered [[Cortico-basal ganglia-thalamo-cortical loop|cortico-basal ganglia]] circuits. The human allele of the FOXP2 gene was transferred into the mouse embryos through [[homologous recombination]] to create humanized FOXP2 mice. The human variant of FOXP2 also had an effect on the exploratory behavior of the mice. In comparison to knockout mice with one non-functional copy of ''FOXP2'', the humanized mouse model showed opposite effects when testing its effect on the levels of dopamine, plasticity of synapses, patterns of expression in the striatum and behavior that was exploratory in nature.<ref name="Enard_2009" />

When FOXP2 expression was altered in mice, it affected many different processes including the learning motor skills and the plasticity of synapses. Additionally, FOXP2 is found more in the [[Cerebral cortex#Layer VI|sixth layer]] of the cortex than in the [[Cerebral cortex#Layer V|fifth]], and this is consistent with it having greater roles in sensory integration. FOXP2 was also found in the [[medial geniculate nucleus]] of the mouse brain, which is the processing area that auditory inputs must go through in the thalamus. It was found that its mutations play a role in delaying the development of language learning. It was also found to be highly expressed in the Purkinje cells and cerebellar nuclei of the cortico-cerebellar circuits. High FOXP2 expression has also been shown in the spiny neurons that express [[Dopamine receptor D1|type 1 dopamine receptors]] in the striatum, [[substantia nigra]], [[subthalamic nucleus]] and [[ventral tegmental area]]. The negative effects of the mutations of FOXP2 in these brain regions on motor abilities were shown in mice through tasks in lab studies. When analyzing the brain circuitry in these cases, scientists found greater levels of dopamine and decreased lengths of dendrites, which caused defects in [[long-term depression]], which is implicated in motor function learning and maintenance. Through [[EEG]] studies, it was also found that these mice had increased levels of activity in their striatum, which contributed to these results. There is further evidence for mutations of targets of the FOXP2 gene shown to have roles in [[schizophrenia]], [[epilepsy]], [[autism]], [[bipolar disorder]] and intellectual disabilities.<ref name="French_2014">{{cite journal | vauthors = French CA, Fisher SE | title = What can mice tell us about Foxp2 function? | journal = Current Opinion in Neurobiology | volume = 28 | pages = 72–9 | date = October 2014 | pmid = 25048596 | doi = 10.1016/j.conb.2014.07.003 | hdl-access = free | s2cid = 17848265 | hdl = 11858/00-001M-0000-0019-F62D-4 }}</ref>