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 5min 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.
Highlights
We isolated several cDNA clones whose expression was altered in murine primary cultures of embryonic neuron and brain upon stimulation with pentylenetetrazole, a seizure-inducing compound [1]
We demonstrated that Dgcr2-KO mice exhibited reduced general locomotor activity in the open field tests and poor motor coordination in the rotarod test
Our present results further suggested that Dgcr2 expression in the brain, the expression in cerebellar Purkinje cells, plays a role in regulating locomotor activity and coordination
Summary
We isolated several cDNA clones whose expression was altered in murine primary cultures of embryonic neuron and brain upon stimulation with pentylenetetrazole, a seizure-inducing compound [1]. One of the downregulated genes, Dgcr (Sez12) [2], is a mouse homolog of human DGCR2 gene that is located in the human chromosome 22q11.2 region and encodes a C-type lectin-like transmembrane protein. It is known that heterologous microdeletion in chromosome 22q11.2 causes a syndrome termed 22q11.2 deletion syndrome (22q11.2 DS) [3]. 22q11.2 DS includes DiGeorge syndrome, conotruncal anomaly face syndrome, and velocardiofacial syndrome. Common in 22q11.2 DS is growth retardation including delayed motor development [4,5], facial dysmorphia, palatal anomalies, abnormal cerebellar morphology [6,7], and early feeding problems [8,9].
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