Behavioral and anatomical deficits in mice homozygous for a modified beta-amyloid precursor protein gene.
The beta-amyloid precursor protein (beta APP) gene of the mouse was disrupted by inserting into exon 2 a cassette containing a neomycin resistance gene and a putative transcription termination sequence. Contrary to expectation, brain and other tissues from mice homozygous for the insertion still contained beta APP-specific RNA, albeit at a level 5- to 10-fold lower than wild type and lacking the disrupted exon, which had been spliced out. The brain contained shortened beta APP-specific protein at a low level. Mutant mice were severely impaired in spatial learning and exploratory behavior and showed increased incidence of agenesis of the corpus callosum.
Müller
U
U
Institut für Molekularbiologie I, Universität Zürich, Switzerland.
Cristina
N
N
Li
Z W
ZW
Wolfer
D P
DP
Lipp
H P
HP
Rülicke
T
T
Brandner
S
S
Aguzzi
A
A
Weissmann
C
C
D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D001522:Behavior, Animal; D001921:Brain / Q000473:pathology*; D005091:Exons / Q000235:genetics; D005106:Exploratory Behavior; D005260:Female; D015870:Gene Expression; D006720:Homozygote; D007858:Learning; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D012333:RNA, Messenger / Q000032:analysis; D013037:Spatial Behavior
D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger