Localization of the gene for the vitamin B12 binding protein,transcobalamin II,near the centromere on mouse chromosome 11, linked with the hemoglobin alpha-chain locus

Somatic cell hybrids, recombinant inbred (RI) mouse strains, and backcross breeding experiments were used to locate the gene of transcobalamin II (Tcn-2), the vitamin B12 binding protein in mouse serum. TCN-2 was found to be a useful genetic marker in the somatic cell hybrids. Selected hybrid clones were derived from fusions between GR mouse cells and the Chinese hamster cell line E36. Analysis of mouse specific chromosomal enzyme markers in relationship to TCN-2 secretion, in the hybrid clones, provided provisional evidence for assignment of the Tcn-2 locus to chromosome 11. The strain distribution pattern of the TCN-2 variants S and F in the RI series CXS, constructed from the cross of BALB/cHeA (TCN-2S) with STS/A (TCN-2F), implied a close linkage with the hemoglobin alpha-chain locus (Hba) on chromosome 11. Backcross breeding using inbred strains confirmed these findings and located the Tcn-2 gene closest to the centromere, linked with waved 2 (wa-2) and Hba with recombination frequencies of 6.9 and 19.2% each. The linkage group Tcn-2/wa-2/Hba was established.This work was supported by Swiss National Science Foundation Grants 3.023-0.81 and 3.728-0.80, Fritz Hoffmann-La Roche Stiftung 173, the Prof. Dr. Max Cloëtta Foundation, and the Kantonale Zürcher Liga für krebsbekämpfung, Switzerland. M. Prochazka was supported by the Postgraduate Training Program for Experimental Medicine and Biology of the University of Zürich, Switzerland.