Lack of detectable kinetochores on some chromosomes in mouse x human hybrids.

When treated with an anti-kinetochore antibody present in the sera of scleroderma (var. CREST) patients, most chromosomes exhibit kinetochore dots at the position of the centromere. In this paper we report that some chromosomes in the mouse x human somatic cell hybrid fail to show these dots. In the early passages in a hybrid, HYG-1, the frequency of such chromosomes was higher (0.85%) than in later passages (0.45%) studied after five months of continuous culturing. In parallel, the mean number of human chromosomes in the hybrid also dropped. The somewhat hypodiploid parental cell lines, when similarly treated, showed only a rare chromosome without kinetochore dots. Immunoblots of the proteins showed that the sera used for kinetochore detection recognized all major centromere proteins (CENPs). Electron microscopy of some offlying metaphase chromosomes in another hybrid, HR61, exhibited a lack of trilamellar kinetochores. This study suggests that akinetochoric chromosomes might provide a novel mechanism responsible for chromosome loss and genesis of aneuploidy. In early passages, some cells in the hybrid showed detached kinetochores. These autonomous kinetochores could be seen in clusters and involved some mouse chromosomes also. Potential significance of these autonomous kinetochores in generating compound centromeres is discussed.