Chen Fangluo, Saqib Muzna, Terrillion Chantelle E, Miranda Chloe, Sarver Dylan C, Scafidi Joseph, Wong G William
Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Physiol Behav. 2025 Mar 15;291:114799. doi: 10.1016/j.physbeh.2025.114799. Epub 2025 Jan 4.
C1q/TNF-related protein 14 (CTRP14), also known as C1q-like 1 (C1QL1), is a synaptic protein predominantly expressed in the brain. It plays a critical role in the formation and maintenance of the climbing fiber-Purkinje cell synapses, ensuring that only one single winning climbing fiber from the inferior olivary neuron synapses with the proximal dendrites of Purkinje cells during the early postnatal period. Loss of CTRP14/C1QL1 results in incomplete elimination of supernumerary climbing fibers, leading to multiple persistent climbing fibers synapsing with the Purkinje cells. While this deficit impairs oculomotor learning in adult mice, the impact of CTRP14 deficiency on motor function throughout adulthood has not been examined. Here, we conduct behavioral tests on a constitutive Ctrp14 knockout (KO) mouse model to determine whether CTRP14 is required for motor learning and function in mice across the lifespan. We show that CTRP14 deficiency does not affect grip strength, nor sprint and endurance running, in young and old mice of either sex. We performed accelerated rotarod tests on mice at 6, 12, and 18 months old to assess motor coordination and learning. No significant differences were observed between WT and Ctrp14-KO mice of either sex across the lifespan. Lastly, we performed complex running wheel tests to detect latent motor deficits and found that aged Ctrp14-KO mice have intact motor skills. Despite some limitations of the study, our data suggest that CTRP14 is dispensable for gross motor skills, coordination, and learning throughout adulthood based on the specific tests performed.
C1q/TNF相关蛋白14(CTRP14),也称为C1q样蛋白1(C1QL1),是一种主要在大脑中表达的突触蛋白。它在攀爬纤维 - 浦肯野细胞突触的形成和维持中起关键作用,确保在出生后早期只有一条来自下橄榄核神经元的获胜攀爬纤维与浦肯野细胞的近端树突形成突触。CTRP14/C1QL1的缺失导致多余攀爬纤维不能完全消除,从而导致多条持续的攀爬纤维与浦肯野细胞形成突触。虽然这种缺陷会损害成年小鼠的动眼神经学习能力,但CTRP14缺乏对整个成年期运动功能的影响尚未得到研究。在此,我们对组成型Ctrp14基因敲除(KO)小鼠模型进行行为测试,以确定CTRP14是否是小鼠整个生命周期中运动学习和功能所必需的。我们发现,CTRP14缺乏对年轻和老年雌雄小鼠的握力、短跑和耐力跑均无影响。我们对6、12和18月龄的小鼠进行了加速转棒试验,以评估运动协调性和学习能力。在整个生命周期中,野生型和Ctrp14基因敲除小鼠在运动协调性和学习能力上均未观察到显著差异。最后,我们进行了复杂的跑轮试验以检测潜在的运动缺陷,发现老年Ctrp14基因敲除小鼠的运动技能完好无损。尽管本研究存在一些局限性,但根据所进行的特定测试,我们的数据表明CTRP14在整个成年期的总体运动技能、协调性和学习中并非必需。