Abstract
We are investigating insulin gene expression in transgenic mice carrying multiple copies of the human preproinsulin gene. An 8.8 kb EcoRI-Hind III human genomic DNA fragment containing the insulin gene was introduced into 1-cell mouse embryos by pronuclear microinjection. This DNA fragment includes 2kb of 5′ and 5.5kb of 3′ human flanking sequences. Two lines of insulin transgenie mice have been established that differ in copy number of the human gene: one line has 4 copies integrated per cell, the other 16 copies per cell. Total serum insulin levels were determined by RIA (Cambridge Medical). Fasted insulin levels in transgenie mice (mean ± SEM = 0.48 ± 0.08 ng/ml, n=37) were significantly higher than in controls (0.10 ± 0.01 ng/ml, n=10; p < 0.001). Comparing the 2 transgenic lines, there was considerable variation in insulin levels but those animals with more copies of the human gene have higher insulin levels (0.74 ± 0.20 ng/ml, n=11) than those with fewer copies (0.37 ± 0.06 ng/ml, n=26). Both lines have significantly higher insulin levels than control (p < 0.01). This is in contrast with previously reported insulin transgenics (Bucchini et al, PNAS 83:2511) in which insulin was not overexpressed. In this model system, insulin gene expression correlates with gene copy number, suggesting a direct gene dosage effect.
Article PDF
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Marban, S., Gearhart, J. HYPERINSULINEMIA IN TRANSGENIC MICE CARRYING MULTIPLE COPIES OF THE HUMAN INSULIN GENE: EVIDENCE FOR A GENE DOSAGE EFFECT. Pediatr Res 21 (Suppl 4), 344 (1987). https://doi.org/10.1203/00006450-198704010-01063
Issue Date:
DOI: https://doi.org/10.1203/00006450-198704010-01063