Abstract
We have established transgenic mice that constitutively overproduce the signal sequence and the 99-amino-acid carboxyl-terminal region of the human β-amyloid precursor protein. The transgenic mice strongly expressed the transgene in multiple tissues under the control of a cytomegalovirus enhancer/chick β-actin promoter. There were exceptionally high levels of β- amyloid peptides in the plasma (approximately 17 times or more compared with the human plasma level). Although some transgenic mice from one founder line developed amyloidosis in the intestine, no neuropathology was found in transgenic mice up to age 29 months. Given the absence of cerebral β- amyloidosis despite extremely high levels of circulating β-amyloid peptides in the transgenic mice, the results suggest that local cerebral metabolism of β-amyloid precursor protein may play a predominant role in cerebral β- amyloidosis in transgenic mice. Such transgenic mice may be useful for the investigation of the etiology of the disease and for the establishment of therapeutic strategies.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 219-227 |
| Number of pages | 9 |
| Journal | American Journal of Pathology |
| Volume | 149 |
| Issue number | 1 |
| State | Published - Jul 1996 |
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ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
High levels of circulating β-amyloid peptide do not cause cerebral β- amyloidosis in transgenic mice. / Fukuchi, Ken Ichiro; Ho, Libin; Younkin, Steven G; Kunkel, Dennis D.; Ogburn, Charles E.; LeBoeuf, Renee C.; Furlong, Clement E.; Deeb, Samir S.; Nochlin, David; Wegiel, Jerzy; Wisniewski, Henry M.; Martin, George M.
In: American Journal of Pathology, Vol. 149, No. 1, 07.1996, p. 219-227.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - High levels of circulating β-amyloid peptide do not cause cerebral β- amyloidosis in transgenic mice
AU - Fukuchi, Ken Ichiro
AU - Ho, Libin
AU - Younkin, Steven G
AU - Kunkel, Dennis D.
AU - Ogburn, Charles E.
AU - LeBoeuf, Renee C.
AU - Furlong, Clement E.
AU - Deeb, Samir S.
AU - Nochlin, David
AU - Wegiel, Jerzy
AU - Wisniewski, Henry M.
AU - Martin, George M.
PY - 1996/7
Y1 - 1996/7
N2 - We have established transgenic mice that constitutively overproduce the signal sequence and the 99-amino-acid carboxyl-terminal region of the human β-amyloid precursor protein. The transgenic mice strongly expressed the transgene in multiple tissues under the control of a cytomegalovirus enhancer/chick β-actin promoter. There were exceptionally high levels of β- amyloid peptides in the plasma (approximately 17 times or more compared with the human plasma level). Although some transgenic mice from one founder line developed amyloidosis in the intestine, no neuropathology was found in transgenic mice up to age 29 months. Given the absence of cerebral β- amyloidosis despite extremely high levels of circulating β-amyloid peptides in the transgenic mice, the results suggest that local cerebral metabolism of β-amyloid precursor protein may play a predominant role in cerebral β- amyloidosis in transgenic mice. Such transgenic mice may be useful for the investigation of the etiology of the disease and for the establishment of therapeutic strategies.
AB - We have established transgenic mice that constitutively overproduce the signal sequence and the 99-amino-acid carboxyl-terminal region of the human β-amyloid precursor protein. The transgenic mice strongly expressed the transgene in multiple tissues under the control of a cytomegalovirus enhancer/chick β-actin promoter. There were exceptionally high levels of β- amyloid peptides in the plasma (approximately 17 times or more compared with the human plasma level). Although some transgenic mice from one founder line developed amyloidosis in the intestine, no neuropathology was found in transgenic mice up to age 29 months. Given the absence of cerebral β- amyloidosis despite extremely high levels of circulating β-amyloid peptides in the transgenic mice, the results suggest that local cerebral metabolism of β-amyloid precursor protein may play a predominant role in cerebral β- amyloidosis in transgenic mice. Such transgenic mice may be useful for the investigation of the etiology of the disease and for the establishment of therapeutic strategies.
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UR - http://www.scopus.com/inward/citedby.url?scp=8944228919&partnerID=8YFLogxK
M3 - Article
C2 - 8686746
AN - SCOPUS:8944228919
VL - 149
SP - 219
EP - 227
JO - American Journal of Pathology
JF - American Journal of Pathology
SN - 0002-9440
IS - 1
ER -