A mouse model of familial amyloidotic polyneuropathy type I homozygous for the mutant transthyretin gene

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• 作者：Yokoi ; K. ; Ito ; S. ; Mabuchi ; T. ; Miyakawa ; K. ; Palha ; J. A. ; Iijima ; H. ; Tsukahara ; S. ; Blaner ; W. S. ; et. al.
• 刊名：Neuromuscular Disorders
• 出版年：1996
• 出版时间：February, 1996
• 年：1996
• 卷：6
• 期：1, Supplement 1
• 页码：S32
• 全文大小：79.2 K

文摘

To generate a closer model of familial amyloidotic polyneuropathy (FAP) type I and to elucidate the function of the human variant TTR, we introduced the human mutant transthyretin (ttr) gene, that is responsible for FAP type I, into the TTR-deficient mice generated through gene targeting. The introduced human mutant gene (6.0-hMet30) contained 6 kb of its own upstream region. The serum levels of human TTR Met 30 in these transgenic mice varied from 20 to 60 mg/dl. In these transgenic mice, amyloid composed of human TTR began to deposit at the age 11 months. The deposition of amyloid was independent of the serum levels of human TTR. There appeared to be no significant difference in the onset, progression, and tissue distribution of amyloid deposition between the TTR-deficient and control wild type transgenic mice carrying 6.0-hMet30. The above observation is consistent with the observation that the FAP patients homozygous for the mutant ttr gene do not show more severe symptoms or earlier onset than those heterozygous for the mutant gene. The TTR-deficient mouse carrying 6.0-hMet30 should be useful as a closer model of FAP homozygous for the mutant ttr gene. However, these mice have not yet developed peripheral neuropathy.