THE MOUSE APLP2 GENE - CHROMOSOMAL LOCALIZATION AND PROMOTER CHARACTERIZATION

Senile plaques are primarily comprised of deposits of the beta-amyloid protein derived from larger amyloid precursor proteins (APPs). APP is a member of a gene family, including amyloid precursor-like proteins APLP1 and APLP2. Using interspecific mouse backcross mapping, we local ized the mouse APLP2 gene to the proximal region of mouse chromosome 9 , syntenic with a region of human 11q. We cloned an similar to 1.2-kil obase mouse genomic fragment containing the APLP2 gene promoter. The A PLP2 promoter lacks a typical TATA box, is CC-rich, and contains sever al sequences for transcription factor binding. S1 nuclease protection analysis revealed the presence of multiple transcription start sites. The lack of a TATA box, the presence of a high GC content, and multipl e transcription start sites place the APLP2 promoter in the class of p romoters of ''housekeeping genes.'' Regulatory regions within the prom oter were assayed by transfection of mouse N2a and Ltk(-) cells with c onstructs containing progressive 5'-deletions of the APLP2 promoter fu sed to the bacterial chloramphenicol acetyl transferase (CAT) reporter gene. A minimal region that includes sequences 99 bp upstream of the predominant transcription start site of the APLP2 promoter was suffici ent to direct high levels of CAT expression.