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Title: | Effects of the major formaldehyde catalyzer ADH5 on phenotypes of fanconi anemia zebrafish model |
Authors: | Mu, Anfeng https://orcid.org/0000-0001-8563-8625 (unconfirmed) Cao, Zimu Huang, Denggao Hosokawa, Hiroshi Maegawa, Shingo Takata, Minoru https://orcid.org/0000-0002-4926-3675 (unconfirmed) |
Author's alias: | 牟, 安峰 曹, 子牧 細川, 浩 前川, 真吾 髙田, 穰 |
Keywords: | Fanconi anemia ADH5 Formaldehyde ALDH2 FANCD2 UBE2T |
Issue Date: | Oct-2023 |
Publisher: | Springer Nature |
Journal title: | Molecular Biology Reports |
Volume: | 50 |
Issue: | 10 |
Start page: | 8385 |
End page: | 8395 |
Abstract: | [Background] Fanconi anemia (FA) is a devastating hereditary disorder for which we desperately need a novel therapeutic strategy. It is caused by mutations in one of at least 22 genes in the FA pathway and is characterized by developmental abnormalities, bone marrow failure, and cancer predisposition. The FA pathway is required for the efficient repair of damaged DNA, including interstrand cross-links (ICL). Recent studies indicate formaldehyde as an ultimate endogenous cause of DNA damage in FA pathophysiology. Formaldehyde can form DNA adducts as well as ICLs by inducing covalent linkages between opposite strands of double-stranded DNA. [Methods and results] In this study, we generated a disease model of FA in zebrafish by disrupting the ube₂t or fancd₂ gene, which resulted in a striking phenotype of female-to-male sex reversal. Since formaldehyde is detoxified from the body by alcohol dehydrogenase₅ (ADH₅), we generated fancd₂⁻/⁻/adh₅⁻/⁻ zebrafish. We observed a body size reduction and a lower number of mature spermatozoa than wild-type or single knockout zebrafish. To evaluate if increased activity in ADH₅ can affect the FA phenotype, we overexpressed human ADH₅ in fancd₂⁻/⁻zebrafish. The progress of spermatogenesis seemed to be partially recovered due to ADH₅ overexpression. [Conclusions] Our results suggest potential utility of an ADH₅ enzyme activator as a therapeutic measure for the clearance of formaldehyde and treatment of FA. |
Rights: | This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: http://dx.doi.org/10.1007/s11033-023-08696-8 The full-text file will be made open to the public on 24 August 2024 in accordance with publisher's 'Terms and Conditions for Self-Archiving'. This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。 |
URI: | http://hdl.handle.net/2433/285761 |
DOI(Published Version): | 10.1007/s11033-023-08696-8 |
PubMed ID: | 37615925 |
Appears in Collections: | Journal Articles |
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