Targeted mutation of NCAM to produce a secreted molecule resulting in a dominant embryonic lethality

he neural cell adhesion molecule (NCAM) is a membrane associated glycoprotein and a member of the immunoglobulin superfamily. NCAM is broadly expressed and interacts both homophilically and heterophilically. Ncam transcripts can be alternative spliced to produce various protein isoforms, the most abundant being NCAM180, NCAM140, and NCAM120. Previous targeted mutagenesis in mouse embryonic stem (ES) cells of the Ncam locus, has resulted in a null mutation and a NCAM180 isoform deletion. Mice generated by these mutations are viable and fertile.;Two strategies were used to study the importance of NCAM's membrane attachment. In the transgenic approach, a...