Impaired motor coordination in mice lacking neural recognition molecule NB‐3 of the contactin/F3 subgroup

Abstract

The neural recognition molecule NB-3, which belongs to the contactin subgroup of the immunoglobulin superfamily, is expressed exclusively in the nervous system and mainly upregulated at the early postnatal stage during mouse brain development. The expression of NB-3 in the cerebellum increases until adulthood. In contrast, the expression in the cerebrum declines to a low level after postnatal day 7. To characterize the functional roles of NB-3 in vivo, we generated NB-3-deficient mice by substituting a part of the NB-3 gene with the beta-galactosidase (Lac Z) gene. Complete overlap of the Lac Z expression in the heterozygous mouse brain with the NB-3 immunostaining pattern in the rat cerebellum and with the previously reported pattern of in situ hybridization of NB-3 transcripts indicated that Lac Z expression reflects the expression of NB-3 in the mouse brain. NB-3-deficient mice were viable and fertile. The formation and organization of all nuclei and layers throughout the brains of mutant mice appeared normal. Behavioral tests to examine motor function showed that the mice deficient for NB-3 were slow to learn to stay on the rotating rod in the rotorod test during repeated trials, and that they displayed dysfunction of equilibrium and vestibular senses in the wire hang and horizontal rod-walking tests. In contrast, the mutant mice showed no difference of grasp force from the wild-type mice. Thus, NB-3-deficient mice are impaired in motor coordination.

Prehistoric genomes reveal the genetic foundation and cost of horse domestication

“…Defects in these genes are associated with several forms of myopathies (41), including limb-girdle muscular dystrophy 2F, which causes limb musculature wasting and locomotory troubles in juvenile individuals. Additionally, many selected genes are involved in balance and motor coordination, including VRK1 and TCTN1, with defects associated with underdevelopment of the cerebellum, motor dysfunction and muscle hypotonia (42,43), and CNTN6, loss of which causes motor coordination and equilibrium impairment in KO mice (44). This set of genes also includes a member of the collagen protein family, COL22A1, which localizes to myotendinous and articular junctions (45).…”

The protein tyrosine phosphatases PTPRZ and PTPRG bind to distinct members of the contactin family of neural recognition molecules

“…Interestingly, mice deficient in either PTPRG or CNTN6 exhibit impaired motor coordination during rod walking and string tests (4,24). These similar phenotypes suggest that the physical association of PTPRG and CNTN6 may be important for acquiring proper motor functions.…”

Developmental role of the cell adhesion molecule Contactin-6 in the cerebral cortex and hippocampus

“…3B), consistent with previous reports. 16 These results suggest that Cntn6 is not involved in the regulation of gross cortical morphology but rather in the fine-tuning of specific features of cortical development, such as the orientation of dendritic outgrowth. Previous reports suggest that Cntn6 does not affect the migration of developing pyramidal neurons.…”

“…B57BL/6 and Cntn6 ¡/¡ mice were obtained from Charles River and Nagaoka University, 16 respectively. Mice were maintained on a 12-h light/dark cycle with ad libitum food and water in the animal facility of the Brain Center Rudolf Magnus, Utrecht.…”

“…In the murine brain, the Cntn6 gene is expressed in the cortex, hippocampus, thalamus and cerebellum, [15][16][17] reaching a maximum at P14 and thereafter declining to a constant level in adulthood. 15 The notion that loss of Cntn6 results in inappropriate neurodevelopment is strengthened by the phenotypes identified in nullmutants.…”