MOLECULAR-CLONING AND IN-SITU LOCALIZATION OF THE HUMAN CONTACTIN GENE (CNTN1) ON CHROMOSOME 12Q11-Q12

Chick contactin/F11 (also known as F3 in mouse) is a neuronal cell adh esion molecule of the immunoglobulin (Ig) gene family that is implicat ed in playing a role in the formation of axon connections in the devel oping nervous system. In human brain, contactin was first identified b y amino terminal and peptide sequencing of the lentil-lectin-binding g lycoprotein Gp135. We now report the isolation and characterization of cDNA clones encoding human contactin. Human contactin is composed of six C2 Ig-domains and four fibronectin type III (FNIII) repeats and is anchored to the membrane via a glycosyl phosphatidylinositol moiety, as shown by PI-PLC treatment of cells transfected with contactin cDNA and metabolic labeling with [H-3]ethanolamine. At the amino acid level , h-contactin is 78% identical to chick contactin/F11 and 94% to mouse F3. Independent cDNAs encoding two putative contactin isoforms were i solated and sequenced: h-contactin 1 cDNA encodes a protein with the a mino-terminal sequence of purified Gp135, while the putative h-contact in 2 gene has a deletion of 33 nucleotides that predicts a protein wit h a shortened amino terminus. Northern analysis with a probe common fo r both isoforms detects one mRNA species of approximately 6.6 kb in ad ult human brain. Fluorescence in situ hybridization maps the gene for human contactin to human chromosome 12q11-q12. The h-contactin gene lo cus is thus in close proximity to homeobox 3, integrin subunit alpha 5 , several proto-oncogene genes, a chromosomal breakpoint associated wi th various tumors, and the gene locus for Stickler syndrome. The cloni ng of human contactin now permits the study of its role in disorders o f the human nervous system. (C) 1994 Academic Press, Inc.