Several β-cell specific transgenic mice contained human growth hormone (hGH) cassette to enhance expression of transgene. Unexpectedly, we noticed the ectopic serotonin production in pancreatic -cells of these transgenic mice. Among different mouse lines, we found serotonin production in RIP-CreMgn, MIP-GFP, and MIP-CreER mice. Tph1 expression is highly upregulated in pancreatic islets. We generated the new MIP-Cre mice which express Cre recombinase under the control of mouse Ins1 promoter (MIP). We used two different transgene constructs with or without hGH cassette to confirm its effect on serotonin production. All of four founders of MIP-Cre-hGH expressed Tph1 and serotonin in β-cells, which were not observed in founders of MIP-Cre. These finding suggest that transgenic mice containing hGH cassette should be used carefully in β-cell research.