CTRP10 is required for optimal motor function.

CTRP10, also known as C1QL2, is a secreted protein of the C1q family. In the central nervous system, CTRP10 is predominantly expressed by neurons and oligodendrocytes. Changes in brain expression of CTRP10 are associated with addiction, depression, and psychiatric disorder. CTRP10 also serves as a specific molecular marker for the excitatory neurons in the anterior thalamic nuclei complex, as well as for neurons that control proprioception and fine motor skills. Whether CTRP10 is required for nervous system control of behaviors is unknown. Here, we determine whether and how CTRP10 deficiency adversely impacts mouse behaviors. Constitutive knockout (KO) mice lacking CTRP10 have normal exploratory behaviors, spatial and recognition memory, and sensorimotor gating. While grip strength is preserved, Ctrp10 KO female mice show impaired motor coordination in the rotarod task; motor learning, however, is intact. Beam walk and complex running wheel tasks further indicate striking deficits in fine motor skills, with female KO mice showing markedly more pronounced phenotypes. Transcriptomic analyses show that CTRP10 loss alters biological pathways in the cerebellum and motor cortex related to synaptic organization, cell signaling, mitochondrial respiration, and locomotor behavior. Functional analysis also indicates reduced mitochondrial respiration in the motor cortex of KO mice. These combined changes likely contribute to motor function deficits in our KO animals. Collectively, our data uncover a novel central function of CTRP10 and provide genetic evidence that CTRP10 is required for optimal gross and fine motor function.