Table 1.

Oprm1 knockout (KO) mouse models and opioid analgesia

Knockout (KO) mouse model	Variant			Analgesia
	7TM	1TM	6TM	Morphine	IBNtxA
E1-KOa	Lost	Lost	Retained	Lost	Retained
E11-KOb	Retained	Retained	Lost	Retained	Lost
E1/E11-KOc	Lost	Lost	Lost	Lost	Lost

^aReference (20);

^bReference (1,19);

^cReference (16)

The E1-KO (exon 1 knockout) mice lack all the 7TM (transmembrane) and 1TM variants because of loss of exon 1, but still express 6TM variants. On the other hand, the E11-KO (exon 11 knockout) mice lack all the 6TM variants because of loss of exon 11, but still express 7TM and 1TM variants. The E1/E11-KO (exons 1 & 11 knockout) mice lack all the variants because of loss of both exons 1 and 11. Morphine analgesia was lost in E1-KO and E1/E11-KO mice, but retained in E11-KO mice. In contrast, IBNtxA analgesia was lost in E11-KO and E1/E11-KO, but retained in E1-KO mice. These results suggest that morphine analgesia depends on 7TM variants, and IBNtxA analgesia is mediated through 6TM variants.