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Development of a Hepatocyte-Specific Temporal Genetic Mouse Model Using Albumin Promoter-Driven FlpER2 Expression 利用白蛋白启动子驱动的FlpER2表达建立肝细胞特异性时间遗传小鼠模型
IF 2.4 4区 生物学
genesis Pub Date : 2025-07-09 DOI: 10.1002/dvg.70022
Bin Wang, Jiale Wang, Yang Liu, Gordon He, Yasmin Jahan-Mihan, Yuxi Wang, Jie Hu, Audrey Li, Faheem Muhammad, Yan Bi, Baoan Ji
{"title":"Development of a Hepatocyte-Specific Temporal Genetic Mouse Model Using Albumin Promoter-Driven FlpER2 Expression","authors":"Bin Wang,&nbsp;Jiale Wang,&nbsp;Yang Liu,&nbsp;Gordon He,&nbsp;Yasmin Jahan-Mihan,&nbsp;Yuxi Wang,&nbsp;Jie Hu,&nbsp;Audrey Li,&nbsp;Faheem Muhammad,&nbsp;Yan Bi,&nbsp;Baoan Ji","doi":"10.1002/dvg.70022","DOIUrl":"https://doi.org/10.1002/dvg.70022","url":null,"abstract":"<div>\u0000 \u0000 <p>Tissue-specific gene manipulation using Cre/loxP or Flp/frt recombination systems is a cornerstone of genetically engineered mouse models. In this study, we aim to develop a novel hepatocyte-specific, tamoxifen-inducible Flp mouse line. BAC (bacterial artificial chromosome)-Alb(albumin)-FlpER2(estrogen receptor ligan binding domain) was developed by inserting IRES-FlpER2 cDNA between the translation stop codon and 3′-UTR of the mouse albumin gene in a bacterial artificial chromosome. Upon tamoxifen induction in mice crossed with reporter lines, western blotting, immunohistochemistry, immunofluorescence staining, and X-gal staining (5-bromo-4-chloro-3-indolyl-β-D-galactopyranoside Staining) were used to verify the recombination efficiency and specificity of this mouse model. Recombination was highly efficient and specific in hepatocytes, with no recombination detected in intrahepatic cholangiocytes or other organs in this mouse model. We generated a new tamoxifen-induced hepatocyte-specific mouse model with highly efficient recombination specifically in hepatocytes, and this model can be used to generate tumor model lines.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"63 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144582132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Tracing Early Migratory Neurons in the Developing Nose Using Contactin-2 (Cntn2) CreERT2 利用接触蛋白-2 (Cntn2) CreERT2追踪鼻子发育中的早期迁移神经元
IF 2.4 4区 生物学
genesis Pub Date : 2025-06-28 DOI: 10.1002/dvg.70021
Enrico Amato Jr., Alexis M. Semon, Paolo E. Forni
{"title":"Tracing Early Migratory Neurons in the Developing Nose Using Contactin-2 (Cntn2) CreERT2","authors":"Enrico Amato Jr.,&nbsp;Alexis M. Semon,&nbsp;Paolo E. Forni","doi":"10.1002/dvg.70021","DOIUrl":"https://doi.org/10.1002/dvg.70021","url":null,"abstract":"<p>Neuronal migration during embryonic development is a fundamental process. In the developing nose of rodents, neurons that form during early neurogenic waves in the olfactory placode leave this structure to migrate toward or into the developing brain as part of the migratory mass. This mass includes gonadotropin-releasing hormone-1 (GnRH-1) neurons, pioneer/terminal nerve (TN) neurons, as well as neural crest-derived olfactory glial cells called olfactory ensheathing cells. There have been a limited number of molecular markers available to effectively trace and functionally manipulate the early migratory neurons that originate in the olfactory region. Contactin-2 (Cntn2), also known as transiently expressed axonal surface glycoprotein-1 (TAG-1), has been used to label various developing neuronal populations, including the commissural neurons of the spinal cord, motor neurons, and TN neurons. Previous single-cell RNA sequencing analyses of the developing olfactory system have identified Cntn2 expression in the TN, suggesting that Cntn2 is a suitable molecular marker for studying nasal migratory neurons. To trace Cntn2 expression in the developing olfactory system, we generated an inducible Cntn2CreERT2 mouse line. In this study, we outline how this mouse line can serve as an effective tool for time-controlled chimeric manipulation of specific neuronal populations of interest.</p>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"63 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvg.70021","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144503064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Identification and Classification of Zinc Finger Proteins Encoded in the Genome of an Ascidian 一种海鞘动物基因组锌指蛋白的鉴定与分类
IF 2.4 4区 生物学
genesis Pub Date : 2025-06-27 DOI: 10.1002/dvg.70020
Natsuko Tamura, Yutaka Satou
{"title":"Identification and Classification of Zinc Finger Proteins Encoded in the Genome of an Ascidian","authors":"Natsuko Tamura,&nbsp;Yutaka Satou","doi":"10.1002/dvg.70020","DOIUrl":"https://doi.org/10.1002/dvg.70020","url":null,"abstract":"<div>\u0000 \u0000 <p>Genes encoding C2H2-type zinc finger (ZF) proteins constitute one of the largest gene families in animal genomes. Many C2H2-type ZF domains are used for DNA-binding, and others are used for protein–protein interactions and RNA-binding. In ascidian embryos, a gene regulatory network controlling cell fate decision has been studied extensively. However, because ZF proteins have not been well annotated genome-widely, it has not been clear which ZF proteins are possible regulators for cell fate decision in this animal. Therefore, we tried to identify and classify all genes encoding C2H2-type ZF proteins in the genome of an ascidian in the present study. Because the number of ZF domains often varies among possible orthologous proteins, and because ZF domains are not long enough for molecular phylogenetic analyses in many cases, we extensively utilized other bioinformatics tools for their classification. In addition, we found that many ascidian ZF proteins contain fewer ZF domains than their human orthologs; this finding might be related to the compactness of the ascidian genome.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"63 4","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144492708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Generation of Plexin-B1 Conditional Knockout Mouse With CRISPR/Cas9 Technology 用CRISPR/Cas9技术培养丛蛋白b1条件敲除小鼠
IF 2.4 4区 生物学
genesis Pub Date : 2025-06-25 DOI: 10.1002/dvg.70019
Haofei Ni, Kevin Kelley, Ning Xie, Hongyan Zou, Roland H. Friedel
{"title":"Generation of Plexin-B1 Conditional Knockout Mouse With CRISPR/Cas9 Technology","authors":"Haofei Ni,&nbsp;Kevin Kelley,&nbsp;Ning Xie,&nbsp;Hongyan Zou,&nbsp;Roland H. Friedel","doi":"10.1002/dvg.70019","DOIUrl":"https://doi.org/10.1002/dvg.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>Plexins are axon guidance transmembrane receptors that control cytoskeleton and membrane dynamics in development and adult physiology. As plexins are expressed in multiple cell types in various tissues, floxed alleles that enable conditional deletion are needed to facilitate cell type-specific functional analysis. We report here the generation of a conditional floxed allele of Plexin-B1 (gene symbol <i>Plxnb1</i>) in mouse using CRISPR/Cas9 technology to insert two loxP sites flanking critical exons. Targeting reagents (Cas9 protein, sgRNAs, ssODNs) were delivered into single-cell embryos by electroporation. After screening a total of 128 mouse pups by PCR and Sanger sequencing, two mice were identified carrying both loxP sites in the targeted <i>Plxnb1</i> locus (success rate ~ 1.6%). The usage of Alt-R modified ssODNs increased targeting frequencies at one loxP site, but not the other. We also tested homology directed repair (HDR) enhancer V2 reagent, but addition of the enhancer reduced the viability of mouse embryos. The <i>Plxnb1</i><sup>flox</sup> allele was successfully transmitted through the germline in Mendelian ratios, and effective excision of the floxed region was confirmed by breeding with Cre recombinase strains.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"63 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144482225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Genetic Mechanism That Defines the Characteristic Neurogenesis Patterns in the Neural Plate Using Hes/her Genes During Early Vertebrate Development 在脊椎动物早期发育过程中,利用he /her基因确定神经板中特征性神经发生模式的遗传机制
IF 2.4 4区 生物学
genesis Pub Date : 2025-06-02 DOI: 10.1002/dvg.70015
Takero Ohyanagi, Hiroki Tokizaki, Takehisa Sato, Momo Tsuruoka, Kyo Yamasu
{"title":"Genetic Mechanism That Defines the Characteristic Neurogenesis Patterns in the Neural Plate Using Hes/her Genes During Early Vertebrate Development","authors":"Takero Ohyanagi,&nbsp;Hiroki Tokizaki,&nbsp;Takehisa Sato,&nbsp;Momo Tsuruoka,&nbsp;Kyo Yamasu","doi":"10.1002/dvg.70015","DOIUrl":"https://doi.org/10.1002/dvg.70015","url":null,"abstract":"<p>In the early zebrafish neural plate, proneural cluster domains are defined by surrounding neural progenitor pools (NPPs), generating primary neurogenesis patterns. In each NPP, several Notch-independent <i>Hes/her</i>-type genes are expressed in distinct manners. Previous knockdown (KD) experiments induced ectopic neurogenesis in NPPs where only the targeted <i>her</i> genes were expressed, with other <i>her</i> genes absent, suggesting cooperative functions of Notch-independent <i>her</i> genes. In this study, to overcome the inherent limitations in KD approaches, we knocked out (KO) three <i>her</i> genes, <i>her3</i>, <i>her5</i>, <i>and her11</i>, using genome editing techniques. The resulting mutants exhibited ectopic neurogenesis patterns at the end of gastrulation, similar to those observed in KD experiments. KOs of <i>her5</i> and <i>her11</i> induced ectopic neurogenesis around the midbrain-hindbrain boundary, whereas <i>her3</i> KO led to ectopic neurogenesis in rhombomere 1/2 and r4. In these cases, the expression of other Notch-independent <i>her</i> genes was not affected, except for <i>her11</i>, whose expression depended on <i>her5</i>. Analyses of compound mutants revealed that their phenotypes were essentially the sum of those of individual <i>her</i> mutants, indicating independent suppression of neurogenesis by Notch-independent <i>her</i> genes. In conclusion, different Notch-independent <i>her</i> genes collectively define the characteristic pattern of primary neurogenesis in the neural plate.</p>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"63 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvg.70015","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A Comprehensive Review of Mitochondrial Complex I During Mammalian Oocyte Maturation 哺乳动物卵母细胞成熟过程中线粒体复合体I的研究综述
IF 2.4 4区 生物学
genesis Pub Date : 2025-06-02 DOI: 10.1002/dvg.70017
Nazlican Bozdemir, Ceren Cakir, Ulas Topcu, Fatma Uysal
{"title":"A Comprehensive Review of Mitochondrial Complex I During Mammalian Oocyte Maturation","authors":"Nazlican Bozdemir,&nbsp;Ceren Cakir,&nbsp;Ulas Topcu,&nbsp;Fatma Uysal","doi":"10.1002/dvg.70017","DOIUrl":"https://doi.org/10.1002/dvg.70017","url":null,"abstract":"<p>This review provides a comprehensive overview of Complex I during mammalian oocyte maturation. Complex I (NADH:ubiquinone oxidoreductase) is a crucial member of the electron transport chain and serves two principal functions during oxidative phosphorylation: NADH oxidation and proton pumping. It is located at the inner mitochondrial membrane and consists of 14 core and 31 accessory subunits that are necessary for its function and assembly. Moreover, Complex I is the primary site of reactive oxygen species (ROS) production among the different tissues. In light of the literature, it has been demonstrated that ROS and oxidative stress are significantly important among the various factors that can affect oocyte maturation. Factors such as malnutrition, alcohol use, obesity, PCOS, aging, and smoking are some of the common causes of infertility. Each one of them causes disruption in the equilibrium of the body's redox system and related with oxidative stress. During oocyte maturation, excessive ROS levels are associated with chromosomal errors and developmental insufficiency. In addition, excess oxidative stress adversely affects embryo growth and development and may cause fetal embryopathies with damage to macromolecules in the cytoskeleton. At this particular juncture, Complex I plays a key role in determining ROS production and the success of the oocyte maturation. This review evaluates mitochondrial Complex I's function, structure, and its crucial role during oocyte maturation.</p>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"63 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvg.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144191160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Zmym2 Alters Expression of Key Craniofacial Genes Zmym2改变颅面关键基因的表达
IF 2.4 4区 生物学
genesis Pub Date : 2025-05-30 DOI: 10.1002/dvg.70018
Karyn Jourdeuil, Karen M. Neilson, Andre L. P. Tavares, Sally A. Moody
{"title":"Zmym2 Alters Expression of Key Craniofacial Genes","authors":"Karyn Jourdeuil,&nbsp;Karen M. Neilson,&nbsp;Andre L. P. Tavares,&nbsp;Sally A. Moody","doi":"10.1002/dvg.70018","DOIUrl":"https://doi.org/10.1002/dvg.70018","url":null,"abstract":"<div>\u0000 \u0000 <p>To identify novel Six1-interacting proteins, we previously screened the fly interactome for Sine oculis-binding partners whose orthologues are also expressed in <i>Xenopus</i> embryos. We identified a zinc-finger MYM-containing protein—Zmym2—based on its sequence similarity in a few domains also found in the <i>Drosophila</i> and vertebrate Sine oculis-binding proteins (Sobp). Because recent studies established Zmym2 as a transcriptional repressor that interacts with Six4 during renal development, herein we assessed whether it interacts with Six1, can modify Six1's transcriptional activity, and is involved in cranial neural crest or placode gene expression. Although during early development Zmym2 is expressed in many of the same tissues as Six1 and contains several domains also found in Sobp, we did not detect any interaction by co-immunoprecipitation and did not detect any effect on Six1 + Eya1 transcriptional activity in cultured cells. Nonetheless, increasing the level of Zmym2 in embryos resulted in broader expression domains of neural border, neural tube and neural crest genes, and smaller placode gene domains. These results suggest that although Zmym2 is unlikely to be a <i>bone fide</i> Six1 interacting protein, it appears to indirectly antagonize Six1 function during cranial placode development, promoting neural plate and neural crest gene expression.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"63 3","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144179070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Application of scRNA-Seq in Heart Development and Regeneration scRNA-Seq在心脏发育和再生中的应用
IF 2.4 4区 生物学
genesis Pub Date : 2025-04-29 DOI: 10.1002/dvg.70013
Junying Gao, Lindong Yu, Haoran Qi, Jun Qi, Zhaodi Zheng
{"title":"The Application of scRNA-Seq in Heart Development and Regeneration","authors":"Junying Gao,&nbsp;Lindong Yu,&nbsp;Haoran Qi,&nbsp;Jun Qi,&nbsp;Zhaodi Zheng","doi":"10.1002/dvg.70013","DOIUrl":"https://doi.org/10.1002/dvg.70013","url":null,"abstract":"<div>\u0000 \u0000 <p>Single-cell RNA sequencing (scRNA-seq) is a rapidly developing and useful technique for elucidating biological mechanisms and characterizing individual cells. Tens of millions of patients worldwide suffer from heart injuries and other types of heart disease. Neonatal mammalian hearts and certain adult vertebrate species, such as zebrafish, can fully regenerate after myocardial injury. However, the adult mammalian heart is unable to regenerate the damaged myocardium. scRNA-seq provides many new insights into pathological and normal hearts and facilitates our understanding of cellular responses to cardiac injury and repair at different stages, which may provide critical clues for effective therapies for adult heart regeneration. In this review, we summarize the application of scRNA-seq in heart development and regeneration and describe how important molecular mechanisms can be harnessed to promote heart regeneration.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"63 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888913","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Excluding the Genomic Location of Pax2 Regulatory Elements for the Developing Mouse Eye 排除发育中的小鼠眼睛Pax2调控元件的基因组位置
IF 2.4 4区 生物学
genesis Pub Date : 2025-04-29 DOI: 10.1002/dvg.70016
Tzu-Hua Ho, Daniela Santamaria-Munoz, Hollin Hamelynck, Anna La Torre, Tom Glaser, Nadean L. Brown
{"title":"Excluding the Genomic Location of Pax2 Regulatory Elements for the Developing Mouse Eye","authors":"Tzu-Hua Ho,&nbsp;Daniela Santamaria-Munoz,&nbsp;Hollin Hamelynck,&nbsp;Anna La Torre,&nbsp;Tom Glaser,&nbsp;Nadean L. Brown","doi":"10.1002/dvg.70016","DOIUrl":"https://doi.org/10.1002/dvg.70016","url":null,"abstract":"<p>The <i>Pax2</i> transcription factor is activated uniformly in the optic vesicle/cup, but becomes progressively restricted to the forming optic disc and stalk. In the eye, it is not known how <i>Pax2</i> expression is regulated and progressively restricted, in part because no <i>Pax2</i> regulatory elements have been identified for this organ. Multiple Pax2-Cre mouse transgenic lines have been produced, but essentially none of these Cre recombinase drivers are active in the visual system. Only Tg(BAC-Pax2-cre)<sup>Akg</sup> mice have been reported to express Cre in a subset of postnatal retinal astrocytes. We confirm this observation and demonstrate ectopic expression in branchial arches, extraocular muscles, and a subset of GABAergic amacrine cells. Our findings suggest that major eye enhancer(s) for mouse <i>Pax2</i> reside outside the &gt; 180 kb genomic segment delimited by <i>Pax2</i> BAC transgenes.</p>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"63 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/dvg.70016","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Generation of Myeloid-Specific Bmal1 Knockout Mice and Identification of Bmal1-Regulated Ferroptosis in Macrophages 骨髓特异性Bmal1敲除小鼠的产生和巨噬细胞中Bmal1调控的铁凋亡的鉴定
IF 2.4 4区 生物学
genesis Pub Date : 2025-04-08 DOI: 10.1002/dvg.70014
Qing Chen, Wenyi Wang, Weijun Fang, Lianhua Qin, Jie Wang, Xiaochen Huang, Sha Pan, Ruijuan Zheng
{"title":"Generation of Myeloid-Specific Bmal1 Knockout Mice and Identification of Bmal1-Regulated Ferroptosis in Macrophages","authors":"Qing Chen,&nbsp;Wenyi Wang,&nbsp;Weijun Fang,&nbsp;Lianhua Qin,&nbsp;Jie Wang,&nbsp;Xiaochen Huang,&nbsp;Sha Pan,&nbsp;Ruijuan Zheng","doi":"10.1002/dvg.70014","DOIUrl":"https://doi.org/10.1002/dvg.70014","url":null,"abstract":"<div>\u0000 \u0000 <p>Circadian clocks have a fundamental role in many physiological processes. Bmal1 (basic helix–loop–helix ARNT like 1) is a central master circadian clock gene. The global <i>Bmal1</i> knockout mice were shown to have a loss of circadian rhythms, acceleration of aging, and shortened life span. However, global <i>Bmal1</i> knockout mice did not exactly reflect the Bmal1 function in specific cell or tissue types. To address the importance of circadian rhythms in macrophages, we generated myeloid-specific <i>Bmal1</i> knockout mice. The efficacy of <i>Bmal1</i> gene deletion in macrophages was identified at DNA, transcription, protein levels, and function. In contrast to global <i>Bmal1</i> knockout mice, <i>Bmal1</i><sup><i>flox/flox</i></sup> and <i>Bmal1</i><sup><i>mye−/−</i></sup> mice did not exhibit aging phenotypes. However, the deletion of <i>Bmal1</i> resulted in a loss of rhythmic expression of the circadian genes in macrophages. RNA-Seq revealed that Bmal1 regulated the expression of cell death-related genes in macrophages. Furthermore, these genes have been identified as clock-controlled genes in rhythmic cell models, and Bmal1 controlled the rhythmic expression of these genes in macrophages. Finally, Bmal1 inhibited RSL3-induced ferroptosis in macrophages through Phgdh. In summary, the model of myeloid-specific <i>Bmal1</i> knockout mice was successfully constructed, providing a tool for the study of the roles of Bmal1 in macrophages and the peripheral circadian clock. Meanwhile, Bmal1 regulates ferroptosis in macrophages.</p>\u0000 </div>","PeriodicalId":12718,"journal":{"name":"genesis","volume":"63 2","pages":""},"PeriodicalIF":2.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143793741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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