TAG-1-deficient mice have marked elevation of adenosine A1 receptors in the hippocampus.
TAG-1 is a neural recognition molecule in the immunoglobulin superfamily that is predominantly expressed in the developing brain. Several lines of evidence suggest that TAG-1 is involved in the outgrowth, guidance, and fasciculation of neurites. To directly assess the function of TAG-1 in vivo, we have generated mice with a deletion in the gene encoding TAG-1 using homologous recombination in embryonic stem cells. Gross morphological analysis of the cerebellum, the spinal cord, and the hippocampus appeared normal in TAG-1-deficient mice. However, TAG-1 (-/-) mice showed the upregulation of the adenosine A1 receptors determined by [(3)H]cyclopentyl-1,3-dipropylxanthine in the hippocampus, and their greater sensitivity to convulsant stimuli than that in TAG-1 (+/+) mice. We suspect that the subtle changes in neural plasticity induced by TAG-1 deficiency during development cause the selective vulnerability of specific brain regions and the epileptogenicity in TAG-1 (-/-) mice.
Fukamauchi
F
F
Department of Molecular Medical Science, Medical Research Institute, Tokyo Medical and Dental University, 2-3-10, Kandasurugadai, Chiyoda-ku, Tokyo, 101-0062, Japan. ff.epi@mri.tmd.ac.jp
Aihara
O
O
Wang
Y J
YJ
Akasaka
K
K
Takeda
Y
Y
Horie
M
M
Kawano
H
H
Sudo
K
K
Asano
M
M
Watanabe
K
K
Iwakura
Y
Y
D000818:Animals; D000906:Antibodies / Q000378:metabolism; D015139:Blotting, Southern; D015153:Blotting, Western; D002448:Cell Adhesion; D015816:Cell Adhesion Molecules, Neuronal; D002531:Cerebellum / Q000378:metabolism; D058969:Contactin 2; D004622:Embryo, Mammalian / Q000378:metabolism; D017353:Gene Deletion; D006624:Hippocampus / Q000378:metabolism*; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008957:Models, Genetic; D016297:Mutagenesis, Site-Directed; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000096:biosynthesis*; D011995:Recombination, Genetic; D012640:Seizures / Q000235:genetics; D013116:Spinal Cord / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D015854:Up-Regulation
D000906:Antibodies; D015816:Cell Adhesion Molecules, Neuronal; C548675:Cntn2 protein, mouse; D058969:Contactin 2; D008562:Membrane Glycoproteins; D018047:Receptors, Purinergic P1