Transgenic mice expressing F3/contactin from the transient axonal glycoprotein promoter undergo developmentally regulated deficits of the cerebellar function.
We have shown that transgenic transient axonal glycoprotein (TAG)/F3 mice, in which the mouse axonal glycoprotein F3/contactin was misexpressed from a regulatory region of the gene encoding the transient axonal glycoprotein TAG-1, exhibit a transient disruption of cerebellar granule and Purkinje cell development [Development 130 (2003) 29]. In the present study we explore the neurobehavioural consequences of this mutation. We report on assays of reproductive parameters (gestation length, litter size and offspring viability) and on somatic and neurobehavioural end-points (sensorimotor development, homing performance, motor activity, motor coordination and motor learning). Compared with wild-type littermates, TAG/F3 mice display delayed sensorimotor development, reduced exploratory activity and impaired motor activity, motor coordination and motor learning. The latter parameters, in particular, were affected also in adult mice, despite the apparent recovery of cerebellar morphology, suggesting that subtle changes of neuronal circuitry persist in these animals after development is complete. These behavioural deficits indicate that the finely coordinated expression of immunoglobulin-like cell adhesion molecules such as TAG-1 and F3/contactin is of key relevance to the functional, as well as morphological maturation of the cerebellum.
Coluccia
A
A
Department of Pharmacology and Human Physiology, Medical School, University of Bari, Policlinico, Piazza Giulio Cesare, I-70124, Bari, Italy.
Tattoli
M
M
Bizzoca
A
A
Arbia
S
S
Lorusso
L
L
De Benedictis
L
L
Buttiglione
M
M
Cuomo
V
V
Furley
A
A
Gennarini
G
G
Cagiano
R
R
D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000096:biosynthesis* / Q000235:genetics; D002526:Cerebellar Diseases / Q000235:genetics / Q000378:metabolism*; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism*; D058969:Contactin 2; D058966:Contactins; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D019957:Motor Skills Disorders / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy
C548674:CNTN2 protein, human; D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D058966:Contactins