In this study, we have shown that the genetic background of different inbred mouse strains has a dramatic impact on the diabetes induced by the deficiency of the transcription factor Hnf1a. Indeed, we found that the typical severe diabetic phenotype that is observed in sensitive strains (e.g. 129S2) is completely suppressed by the genetic variation present in CBA and C3H strains. The gene discussed is HNF1A; the disease is diabetes mellitus.