Abnormal gait, reduced locomotor activity and impaired motor coordination in Dgcr2 -deficient mice

Abstract

It has been suggested that the DGCR2 gene plays a role in the pathogenesis of 22q11.2 deletion syndrome. To analyze its function, we used our Dgcr2-knock-out/EGFP-knock-in mice (Dgcr2-KO mice). At 20-26 weeks of age, approximately 20% of Dgcr2-KO mice showed gait abnormalities with trembling and difficulty in balancing. Footprint test revealed awkward movements in Dgcr2-KO mice soon after they were placed on the floor. Once they started walking, their stride lengths were not different from wild-type mice. In short-term open field test, Dgcr2-KO mice travelled a significantly shorter distance and walked more slowly than wild-type mice during the initial 5 min after being placed in a new environment. In long-term open field test, Dgcr2-KO mice exhibited reduced cage activity compared to wild-type mice on the first day, but not on later days. Dgcr2-KO mice showed reduced latency to fall in the rotarod test, and the latency was not improved in the 3-day test. Histology revealed sparseness of cerebellar Purkinje cells in Dgcr2-KO mice. Our results suggest that Dgcr2 plays a role in motor control related to Purkinje cell function and that the deficiency of DGCR2 contributes at least to some of the symptoms of patients of 22q11.2 deletion syndrome.

In the line-up: deleted genes associated with DiGeorge/22q11.2 deletion syndrome: are they all suspects?

“…Recent studies support a role for Dgcr2 in cortical projection neuron migration and differentiation, apparently as part of a complex that regulates Reelin-dependent phosphorylation of Dab1, Akt, Erk1/2 and subsequent signaling targets [135]. Dgcr2 deficient mice have gait abnormalities, reduced movement, and impaired motor coordination possibly due to loss of cerebellar Purkinje cells [136]. Finally, a DGCR2 missense mutation has been associated with non-syndromic SCZ [137], reinforcing a potential contribution to neural development or function.…”

Transcriptomic underpinnings of high and low mirror aggression zebrafish behaviours

“…Similar to as3mt , the human orthologue of this gene has been linked to schizophrenia [ 52 ]. Dgcr2 knock-out or knockdown mice show substantial locomotor deficits, altered neuronal migration and impaired Purkinje cell function [ 29 , 53 ]. We have previously suggested that Purkinje cell function may control zebrafish aggression [ 54 ] suggesting that this may represent an important node in a neural circuit that can control this behaviour.…”

Motor Stereotypic Behavior Was Associated With Immune Response in Macaques: Insight From Transcriptome and Gut Microbiota Analysis

“…DGCR2 encodes an activity-dependent adhesion protein ( Kajiwara et al, 1996 ) and participates in neurodevelopment ( Maynard et al, 2003 ). Evidence indicated that abnormal behavior and locomotor activity were significantly reduced in DGCR2 knockout mice in open field tests ( Mugikura et al, 2016 ). Additionally, DGCR2 is associated with Schizophrenia ( Shifman et al, 2006 ; Xu et al, 2011 ).…”