Table 1.

Comparison of four genetic models for miR-21

miR-21 genetics	Technology	Promoter	Genetic background*	Phenotype	Tumor driver gene	Changes in cell biology	miR-21 Targets	Reference
Transgenic	tet-off-mediated conditional overexpression	nestin promoter (active in multiple organs of adult animals)	unknown	pre-B lymphoma	miR-21 overexpression (> 10-fold)	increased cell proliferation; decreased apoptosis	ND†	16
Transgenic	global overexpression	cytomegalovirus immediate early enhancer-chicken beta-actin hybrid promoter (CAG, global)	B6C3F1	no tumors in major organs	miR-21 overexpression (4- to 6-fold) alone did not induce tumorigenesis	ND†	Spry1, Spry2, Btg2	17
			B6C3F1x (B6x129)	when crossed with KrasLA2 mice, enhances lung tumorigenesis	mutant Kras	increased cell proliferation; decreased apoptosis; enhanced Ras signaling	Spry1, Spry2, Btg2, Pdcd4, and others
Gene targeting	conventional knockout	NA†	B6x129	without any gross phenotype; suppresses Kras-driven lung tumorigenesis	mutant Kras	no change in proliferation, apoptosis, or Ras signaling	Spry2
Gene targeting	conventional knockout	NA†	B6.129	without any gross phenotype; suppresses chemical-induced skin carcinogenesis; some immune defect when fed with high-fat diet	mutant Hras	slight reduction in proliferation; increased apoptosis; attenuated Ras signaling	Spry1, Pten, Pdcd4, and others	this study

Bold indicates the difference between two knockout models.

^*B6, C57Bl/6; 129, 129/SvEv; B6C3F1, F1 of c57Bl6 x C3H/HeJ.

^†ND, not determined; NA, not applicable.