Gene dosage for isocitrate dehydrogenase in mouse embryos trisomic for chromosome 1.

IT is generally assumed that changes in chromosome number are reflected in gene dosage effects for loci located in the extra or missing chromosomes. Although such effects have been well substantiated in Drosophila1 data for mammalian aneuploidy are scarce. Quantitative gene dosage effects have been demonstrated for several X-linked enzymes in oocytes of mice with X-chromosome aneuploidy2,3 and for malic enzyme in mice with partial trisomy of chromosome 7 (ref. 4). In man, similar effects for superoxide dismutase-1 (W. W. Feaster, L. W. Kwok and C.J.E., unpublished and ref. 5), adenine phosphoribosyltransferase6, purine nucleoside phosphorylase7 and erythrocyte acid phosphatase8 have been observed in cells aneuploid for chromosomes 21, 16, 14 and 2, respectively. Aneuploidy for chromosome 21 also affects responsiveness to interferon9, and XYY cells have been claimed to have increased amounts of H–Y surface antigen10. Since the detection of more than 30 metacentric (Robertsonian translocation) chromosomes in wild and laboratory strains11,12 and the development of a mating scheme which utilises such translocations for the production of aneuploid embryos in relatively high frequencies13,14, the mouse has become particularly useful for gene dosage studies. We have used this system to demonstrate the dosage effect for supernatant isocitrate dehydrogenase (Id-1) which results from trisomy for chromosome 1.