The 5' portion of exon 1 was replaced with corresponding human sequence mutagenized to contain substitution mutations at all 5 phosphorylation sites, Thr7, Ser8, Ser13, Ser17, and Ser38 (human positions). The incorporation of the specific mutations was verified by sequence analysis as well as by Western blot analysis using antibodies directed toward the phosphorylation sites. Northern blot analysis of total brain RNA showed that transcript levels were unaffected in mutant mice. Immunohistochemical analysis of brain tissue showed that while the distribution of protein was conserved in mutant mice, protein levels were reduced in various regions.