TTR exon-humanized mouse optimal for verifying new therapies for FAP

Li, Zhenghua; Kanazashi, Hideki; Tokashiki, Yoshimi; Fujikawa, Rie; Okagaki, Ayaka; Katoh, Sho; Kojima, Kazuyuki; Haruna, Kyoko; Matsushita, Naoko; Ishikawa, Tomo-o; Chen, Hong; Yamamura, Ken‐ichi

doi:10.1016/j.bbrc.2022.02.035

Cited by 1 publication

(2 citation statements)

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“…The amounts of amyloid deposition varied greatly depending on breeding conditions, type of mutation, etc. For example, Sousa et al [29] reported that amyloid deposition was observed in only one out of 25 mice, while we [30][31][32] reported that amyloid deposition was Kohno 1997 [31] Li 2018 [80] Ttr +/+ : The amounts of amyloid deposition varied greatly depending on housing conditions, type of mutation, etc. For example, Sousa et al reported that amyloid deposition was observed only one out of 25 mice, while we reported that amyloid deposition was observed most of mice even though both groups used the same 6.0-hTTRV30M.…”

Section: Correlation Between the Serum Httr Level And Amount Of Amylo...mentioning

confidence: 96%

“…These levels might be too low to test drug efficacy. To produce an ideal mouse model, we created a TTR exon-humanized mouse in which only mouse exons, but not introns, were replaced with the corresponding human exons using genome editing technology [80] . These TTR exon-humanized mice showed normal TTR expression patterns in terms of serum TTR level and spatial-specificity.…”

Section: Application For Evaluation Of Drug Efficacymentioning

confidence: 99%

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Dissecting pathophysiology of a human dominantly inherited disease, familial amyloidotic polyneuropathy, by using genetically engineered mice

Yamamura

2022

Frigid Zone Medicine

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Familial amyloidotic polyneuropathy (FAP) is a type of systemic amyloidosis characterized by peripheral and autonomic neuropathy. Although FAP is a typical autosomal dominant disorder caused by a point mutation in the TTR gene, the average age at onset varies significantly among different countries. This discrepancy clearly suggests that a combination of intrinsic factors as well as extrinsic (environmental) factors shapes the development of FAP. However, these factors are difficult to analyze in humans, because detailed pathologic tissue analysis is only possible at autopsy. Thus, mouse models have been produced and used to disentangle these factors. This review covers the mouse models produced thus far and how these models are applied to analyze intrinsic and extrinsic factors involved in disease development and to test drug efficacy.

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