Evidence map›Paper›PMID 38656880›Full record

ArticleAging2024

Hepatocyte-specific METTL3 ablation by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), resulted in acute liver failure (ALF) and postnatal lethality.

Shihao Huang, Yingchun Li, Bingjie Wang, Zhihao Zhou, Yonglong Li, Lingjun Shen, Jinge Cong, Liuxin Han, Xudong Xiang, Jiawei Xia and 13 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Aging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
0.2field-weighted citation impact, top 46% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

23 authors at 7 institutions in 1 country.

Shihao HuangCancer Research Institute, Experimental Education and Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Yingchun LiCancer Research Institute, Experimental Education and Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Bingjie WangCancer Research Institute, Experimental Education and Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Zhihao ZhouCancer Research Institute, Experimental Education and Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Yonglong LiCancer Research Institute, Experimental Education and Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Lingjun ShenDepartment of Tuberculosis, Yunnan Clinical Medical Center for Infectious Diseases, The Third People's Hospital of Kunming (The Sixth Affiliated Hospital of Dali University), Kunming 650041, China.
Jinge CongCancer Research Institute, Experimental Education and Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Liuxin HanYunnan Clinical Medical Center for Infectious Diseases, The Third People’s Hospital of Kunming (The Sixth Affiliated Hospital of Dali University), Kunming 650041, China.
Xudong XiangDepartment of Thoracic Surgery, Peking University Cancer Hospital Yunnan (Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University), Kunming 650118, China.
Jiawei XiaYunnan Clinical Medical Center for Infectious Diseases, The Third People’s Hospital of Kunming (The Sixth Affiliated Hospital of Dali University), Kunming 650041, China.
Danhua HeCancer Research Institute, Experimental Education and Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Zhanlin ZhaoDepartment of Gastrointestinal Oncology, Peking University Cancer Hospital Yunnan (Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University), Kunming 650118, China.
Ying ZhouCancer Research Institute, Experimental Education and Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Qiwen LiCancer Research Institute, Experimental Education and Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Guanqi DaiCancer Research Institute, Experimental Education and Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Hanzhang ShenYunnan Clinical Medical Center for Infectious Diseases, The Third People’s Hospital of Kunming (The Sixth Affiliated Hospital of Dali University), Kunming 650041, China.
Taoyan LinDepartment of Pharmacy, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Aibing WuCentral People’s Hospital of Zhanjiang, Zhanjiang 524000, China.
Junshuang JiaCancer Research Institute, Experimental Education and Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Dong XiaoCancer Research Institute, Experimental Education and Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China.
Jing LiRadiotherapy Center, the First People’s Hospital of Chenzhou, Xiangnan University, Chenzhou 423000, China.
Wentao ZhaoDepartment of Gastrointestinal Oncology, Peking University Cancer Hospital Yunnan (Yunnan Cancer Hospital, The Third Affiliated Hospital of Kunming Medical University), Kunming 650118, China.
Xiaolin LinSouthern Medical University Hospital of Integrated Traditional Chinese and Western Medicine, Southern Medical University, Guangzhou 510315, China.
Southern Medical University · CNDali University · CNTCM-Intigrated Cancer Center of Southern Medical University · CNPeking University Cancer Hospital · CNCentral People's Hospital of Zhanjiang · CNChenzhou First People's Hospital · CNPeking University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimIn 2019, to examine the functions of METTL3 in liver and underlying mechanisms, we generated mice with hepatocyte-specific METTL3 homozygous knockout (METTL3Δhep) by simultaneously crossing METTL3fl/fl mice with Alb-iCre mice (GPT) or Alb-Cre mice (JAX), respectively. In this study, we explored the potential reasons why hepatocyte-specific METTL3 homozygous disruption by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), resulted in acute liver failure (ALF) and then postnatal lethality. MAIN

methodsMice with hepatocyte-specific METTL3 knockout were generated by simultaneously crossing METTL3fl/fl mice with Alb-iCre mice (GPT; Strain No. T003814) purchased from the GemPharmatech Co., Ltd., (Nanjing, China) or with Alb-Cre mice (JAX; Strain No. 003574) obtained from The Jackson Laboratory, followed by combined-phenotype analysis. The publicly available RNA-sequencing data deposited in the NCBI Gene Expression Omnibus (GEO) database under the accession No.: GSE198512 (postnatal lethality), GSE197800 (postnatal survival) and GSE176113 (postnatal survival) were mined to explore the potential reasons why hepatocyte-specific METTL3 homozygous deletion by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), leads to ALF and then postnatal lethality. KEY

findingsFirstly, we observed that hepatocyte-specific METTL3 homozygous deficiency by Alb-iCre mice (GPT) or by Alb-Cre mice (JAX) caused liver injury, abnormal lipid accumulation and apoptosis. Secondly, we are surprised to find that hepatocyte-specific METTL3 homozygous deletion by Alb-iCre mice (GPT), but not by Alb-Cre mice (JAX), led to ALF and then postnatal lethality. Our findings clearly demonstrated that METTL3Δhep mice (GPT), which are about to die, exhibited the severe destruction of liver histological structure, suggesting that METTL3Δhep mice (GPT) nearly lose normal liver function, which subsequently contributes to ALF, followed by postnatal lethality. Finally, we unexpectedly found that as the compensatory growth responses of hepatocytes to liver injury induced by METTL3Δhep (GPT), the proliferation of METTL3Δhep hepatocytes (GPT), unlike METTL3Δhep hepatocytes (JAX), was not evidenced by the significant increase of Ki67-positive hepatocytes, not accompanied by upregulation of cell-cycle-related genes. Moreover, GO analysis revealed that upregulated genes in METTL3Δhep livers (GPT), unlike METTL3Δhep livers (JAX), are not functionally enriched in terms associated with cell cycle, cell division, mitosis, microtubule cytoskeleton organization, spindle organization, chromatin segregation and organization, and nuclear division, consistent with the loss of compensatory proliferation of METTL3Δhep hepatocytes (GPT) observed SIGNIFICANCE: These findings from this study and other labs provide strong evidence that these phenotypes (i.e., ALF and postnatal lethality) of METTL3Δhep mice (GPT) might be not the real functions of METTL3, and closely related with Alb-iCre mice (GPT), suggesting that we should remind researchers to use Alb-iCre mice (GPT) with caution to knockout gene in hepatocytes

Indexed as

HepatocytesLiver Failure, AcuteMethyltransferasesAnimalsLiverMiceMice, KnockoutMethyltransferasesMettl3 protein, mouseacute liver failure (ALF)Alb-Cre mice (JAX)Alb-iCre mice (GPT)METTL3postnatal lethality

Identifiers

PMID38656880
PMCPMC11087113
OpenAlexW4394994343

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.