To determine the physiological implications of the interaction between RanBP2 and HKI (and other partners), we employed a murine embryonic stem 129Ola cell line with a targeted RanBP2 locus produced by gene-trapping to produce stable inbred (coisogenic) and mixed background lines, respectively (Figure 4A and 4B). Genotyping of 299 F2 offspring revealed a RanBP2+/+:RanBP2+/−:RanBP2−/− distribution (89:210:0) that deviated from the expected Mendelian ratio and supports that the RanBP2−/− mice were embryonically lethal. E12.5 embryos show strong expression of RanBP2 in the optic vesicle and throughout much of the embryo, which had no apparent developmental abnormalities (Figure 4C). In agreement with previous immunocytochemistry analysis [19], the RanBP2 gene is expressed across mature retinal neurons, but expression in ganglion cells of the adult retina was extremely strong (Figure 4D and 4E).