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

Abstract

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 aneuploidy^2,3 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 In man, similar effects for superoxide dismutase-1 (W. W. Feaster, L. W. Kwok and C.J.E., unpublished and ref. 5), adenine phosphoribosyltransferase⁶, purine nucleoside phosphorylase⁷ and erythrocyte acid phosphatase⁸ have been observed in cells aneuploid for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 strains^11,12 and the development of a mating scheme which utilises such translocations for the production of aneuploid embryos in relatively high frequencies^13,14, 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.