Experimental therapy using double humanized mouse model for familial amyloidotic polyneuropathy.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24590404
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human genetics
• Research Institution: Kumamoto University
• Principal Investigator: LI Zhenghua 熊本大学, 生命資源研究支援センター, 特任助教 (80398239)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 分子遺伝学

Outline of Final Research Achievements

We produced three strains of double humanized mice, Rbp4hRBP4: TtrhTTRVal/Val, Rbp4hRBP4: TtrhTTRVal/Met, Rbp4hRBP4: TtrhTTRMet/Met, by replacing mouse Rbp4 and Ttr gene with human RBP4 and normal or mutant TTR gene, respectively. Altough the serum hTTR levels were much lower than those in Tg(6.0-hTTRMet30) or Tg(6.0-hTTRMet30):Ttr-/-, similar amount of amyloid deposition was observed in alimentary tracts. In addition, amyloid deposition was observed in heart and sciatic nerve in Rbp4hRBP4: TtrhTTRVal/Val and Rbp4hRBP4: TtrhTTRMet/Met. Administration of CHF5074 to these mice resulted in increase of serum TTR by stabilizing TTR tetramers and in decrease of amyloid deposition in heart, stomach and sciatic nerve, suggesting that CHF5074 have a preventing effect on amyloid deposition.

Free Research Field

医歯薬学