To test directly whether Alk is involved in regulating behavioral responses to ethanol, we generated Alk knockout (AlkKO) mice by targeting exons 20–21, which encode the juxtamembrane and N-terminal portion of the tyrosine kinase domain (Figure S2). AlkKO mice are fertile, viable, and appear normal, consistent with an independently generated AlkKO line which targets exon 22 and results in a truncated transcript [16]. We were also unable to discern any gross locomotor defects in the AlkKO mice, either under naïve conditions or in response to a saline injection (data not shown). We examined ALK protein expression in the striatum (specifically, nucleus accumbens) of our AlkKO mice and confirmed a loss of full-length ALK protein (Figure 4A), suggesting that we have generated a loss-of-function mutant similar to that described in Bilsland et al. [16]. We next examined AlkKO mice for their behavioral response to ethanol in a loss of righting reflex (LORR) test. Male and female wild-type and homozygous AlkKO mice were tested at two sedating doses of ethanol, 3.6 and 4.0 g/kg. At each dose of ethanol, we observed significant
