Systemic amyloidosis in transgenic mice carrying the human mutant transthyretin (Met 30) gene. Pathological and immunohistochemical similarity to human familial amyloidotic polyneuropathy, type I.
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.
Araki
S
S
Neurological Center, Mitsui Ohmuta Hospital, Fukuoka, Japan.
Yi
S
S
Murakami
T
T
Watanabe
S
S
Ikegawa
S
S
Takahashi
K
K
Yamarnura
K
K
D000367:Age Factors; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry; D017772:Amyloid Neuropathies / Q000145:classification / Q000235:genetics*; D000686:Amyloidosis / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009420:Nervous System / Q000473:pathology; D009928:Organ Specificity; D011228:Prealbumin / Q000235:genetics*; D013045:Species Specificity; D014781:Viscera / Q000473:pathology
D000682:Amyloid; D011228:Prealbumin