Exons 4 and 5 were replaced with modified ones in which nucleotide substitutions results in the amino acid substitutions of lysine with arginine at positions 117, 161 and 162 (p.K117R (c.350_351delAGinsGA), p.K161R and p.K162R (c.482_486delAGAAGinsGGAGA). A loxP site flanked neomycin resistance gene cassette inserted between the two modified exons was removed by Cre-mediated recombination.