To further identify the role of macrophage RGS12 in oral cancer, we used LysmCre;RGS12fl/fl (RGS12 cKO) mice, which were produced by mating LysmCre with RGS12fl/fl mice (Fig. 2f) created previously in our laboratory.31 Surprisingly, with 8-week 4NQO induction, histological examination revealed a phenotype of invasive oral cancer in all RGS12 cKO mice compared with the control Cre mice with dysplasia and carcinoma in situ (CIS) (Fig. 2g). This evidence concerns the gene RGS12 and in situ carcinoma.