Linkage of the murine transforming growth factor alpha gene with Igk, Ly-2, and Fabp1 on chromosome 6

TGF alpha is a mitogenic polypeptide found in the conditioned media of transformed cell lines as well as in various solid tumors. Although its physiological role in normal tissues is uncertain, the autocrine action of TGF alpha on the EGF receptor is postulated to play a role in tumorigenesis. To explore the possibility that pre-existing mouse mutants might have concordance with the mouse TGF alpha locus (Tgfa) we sought to establish the chromosomal localization of the murine TGF alpha gene. Using Southern analysis we have detected NcoI and PvuII RFLPs in the TGF alpha gene of progenitor RI mouse strains. These RFLPs have been used to analyze four different RI sets of DNA and to assign Tgfa to the 35-cM region of chromosome 6. Linkage has been established and the data suggest that the distance between Igk and wa-1 anchor loci may be less than 8 cM and that the gene order for the proximal to mid region of mouse chromosome 6 may be: Ggc-Xmmv27-[Brp-1, Lvp-1, Ms6-4]-[Igk, Ly2, Ly3 Odc-rs5, Rn7s-6, Fabp1]-[Tgfa/wa-1]-IL5-R. Homology of synteny has been further defined between the proximal region of mouse chromosome 6 and with the 2p13-p11 region of human chromosome 2 encompassing TGFA, IGK, CD8A, and FABP1.