Volume 270,
Number 43,
Issue of October 27, 1995 pp. 25475-25480
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
The
Mouse APLP2 Gene
CHROMOSOMAL LOCALIZATION AND PROMOTER CHARACTERIZATION
(Received for publication, May 10,
1995; and in revised form, July 19, 1995)
Cornelia S.
von Koch
,
Debomoy K.
Lahiri
,
Andrew L.
Mammen
,
Neal
G.
Copeland
,
Debra J.
Gilbert
,
Nancy A.
Jenkins
,
Sangram S.
Sisodia
Senile plaques are primarily comprised of deposits of the
-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 localized the mouse APLP2 gene to the
proximal region of mouse chromosome 9, syntenic with a region of human
11q.
We cloned an
1.2-kilobase mouse genomic fragment
containing the APLP2 gene promoter. The APLP2 promoter lacks a typical TATA box, is GC-rich, and contains
several 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 multiple transcription start sites place the APLP2 promoter in the class of promoters of ``housekeeping
genes.''
Regulatory regions within the promoter were assayed by
transfection of mouse N2a and Ltk
cells with
constructs containing progressive 5`-deletions of the APLP2 promoter fused 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 sufficient to direct high levels of CAT expression.