Multiple but different genetic factors underlie enflurane and isoflurane requirements studied through backcross analysis in C57BL and ddN mice.

We performed a classic backcross analysis to examine the basic genetic nature of enflurane (ENF) and isoflurane (ISO) anesthetic requirement in two inbred mice strains, C57BL (BL) and ddN. We have previously reported different ENF and ISO anesthetic requirements in these two strains. BL (n = 22) and ddN (n = 26) mice were used as parents and were reciprocally crossed to produce F1 hybrid mice. Each F1 offspring was crossed to its parent to produce backcross siblings (BF1). Anesthetic end point was determined as the loss of righting reflex. Measurement of anesthetic requirement was performed during 8-12 wk after birth. Although ddN mice showed slightly less resistance to ENF and ISO compared with our previous report, they were more resistant than BL mice. Multivariate regression analysis of parents' and F1 hybrids' data revealed that, while maternal factors and factors on autosomes were related to both anesthetics, the factors on the X chromosome were ENF specific. A wide variation in anesthetic requirements among BF1 progeny suggested multifactorial inheritance. The regression equations obtained did not always predict anesthetic requirement in BF1 progeny. These discrepancies may be due to the epistatic interaction of related genes. We conclude that multiple but different genetic factors are involved in determining ENF and ISO anesthetic requirements in BL and ddN mice.