Systemic amyloidosis in transgenic mice carrying the human mutant transthyretin (Met 30) gene |
| |
Authors: | Shukuro Araki Shigehiro Yi Tatsufumi Murakami Susumu Watanabe Shinichi Ikegawa Kiyoshi Takahashi Ken-ichi Yamarnura |
| |
Institution: | (1) Neurological Center, Mitsui Ohmuta Hospital, Ohmuta, Fukuoka, Japan;(2) First Department of Internal Medicine, Kumamoto University School of Medicine, Kumamoto, Japan;(3) Department of Pathology, Kumamoto University School of Medicine, Kumamoto, Japan;(4) Institute for Medical Genetics, Kumamoto University School of Medicine, Kumamoto, Japan |
| |
Abstract: | To analyze the pathologic processes of amyloid deposition in type I familial amyloidotic polyneuropathy (FAP), mice were made
transgenic by introducing the human mutant transthyretin (TTR) gene(MT-hMet 30). An inbred strain of mouse, C57 BL/6, was
chosen. Transgenic mice were killed using ether anesthesia at 3-mo intervals up to 24 mo after birth. In these transgenic
mice, amyloid deposition started in the gastrointestinal tract, cardiovascular system, and kidneys and extended to various
other organs and tissues with advancing age. The pattern of amyloid deposition was similar to that observed in human autopsy
cases of FAP, except for its absence in the choroid plexus and in the peripheral and autonomic nervous systems.
We extracted the amyloid fibrils from kidneys of these mice with a human mutant TTR gene and analyzed them immunochemically
and electronmicroscopically. Deposited amyloid was shown to be composed of human mutant TTR and mouse serum amyloid P component.
Amyloid fibril from transgenic mice was morphologically and immunohistochemically similar to that of human FAP.
The most striking pathologic feature of the transgenic mice was the absence of amyloid deposition in the peripheral and autonomic
nervous tissues. Thus, other intrinsic factors may be involved in amyloid deposition in the nervous tissues of human FAP. |
| |
Keywords: | Molecular genetics of dominant inheritance familialamyloidotic polyneuropathy (FAP) amyloidosis in transgenic mice human mutant transthyretin (prealbumin) gene amyloid fibril protein |
本文献已被 SpringerLink 等数据库收录! |
|