FASEB bioAdvances最新文献

{"title":"Tumor innervation in cervical cancer: Prognostic insights from myelin-associated risk signatures","authors":"Guoqiang Chen,&nbsp;Zhen Zheng,&nbsp;Qingqing Ji,&nbsp;Ruihua He,&nbsp;Zhouyuan Pan,&nbsp;Yunxia Chen,&nbsp;Yuqing Zhou,&nbsp;Zhihong Wei,&nbsp;Hao Sun,&nbsp;Lixia Feng","doi":"10.1096/fba.2024-00190","DOIUrl":"https://doi.org/10.1096/fba.2024-00190","url":null,"abstract":"<p>The reported frequencies of perineural invasion (PNI) in human cervical cancer, ranging from 7.0% to 35.1%, may underestimate the significant role that nerves play in cervical cancer progression. Neurosecretory factors can promote tumor migration and invasion, even in cases classified as “PNI-negative”. This study aimed to clarify whether tumor innervation influences tumor progression and cervical cancer patient outcomes. We first evaluated the gene signatures of human myelinating Schwann cells (SCs) using the Inferring Pathway Activity and Suppression (IPAS) scoring system to predict the degree of tumor innervation in 304 cervical cancer patients from The Cancer Genome Atlas (TCGA) database. Subsequently, we constructed a myelin-associated risk prognostic signature using LASSO regression analysis. Finally, we obtained a risk score using a quantitative formula and categorized all samples into high- and low-risk score groups. Our results indicated that tumor innervation in cervical cancer is associated with poor patient survival. Higher levels of innervation were correlated with an impaired immune response and reduced expression of immune checkpoints, including PD-L1. The prognostic model demonstrated excellent consistency between predicted and actual survival outcomes. Overall, tumor innervation plays a crucial role in regulating cervical cancer prognosis. The identified prognostic risk signatures offer a valuable tool for risk stratification and prognostic prediction in clinical practice.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Photoperiod influences visceral adiposity and the adipose molecular clock independent of temperature in wild-derived Peromyscus leucopus","authors":"Margaret E. Newport,&nbsp;Paul Wilson,&nbsp;Shanna Lowes,&nbsp;Marthe Behrends,&nbsp;Alexis Coons,&nbsp;Jeff Bowman,&nbsp;Holly E. Bates","doi":"10.1096/fba.2024-00115","DOIUrl":"https://doi.org/10.1096/fba.2024-00115","url":null,"abstract":"<p>Physiology is closely synchronized to daily and seasonal light/dark cycles. Humans artificially extend daylight and experience irregular light schedules, resulting in dysregulation of metabolism and body mass. In rodents, winter-like conditions (cold and short photoperiod) can alter energy balance and adipose tissue mass. To determine if photoperiod alone, independent of temperature, is a strong enough signal to regulate adiposity, we compared the effects of long and short photoperiod at thermoneutrality on adiposity and WAT gene expression in photoperiod-sensitive, F1 generation wild-derived adult male white-footed mice (<i>Peromyscus leucopus</i>). Mice were housed in long-day (16:8 light:dark) or short-day (8:16 light:dark) photoperiod conditions at thermoneutrality (27°C) for 4 weeks with the extended light being provided through artificial lighting. Photoperiod did not impact body weight or calorie consumption. However, mice housed in long photoperiod with extended artificial light selectively developed greater visceral WAT mass without changing subcutaneous WAT or interscapular BAT mass. This was accompanied by a decrease in <i>Adrβ3</i> and <i>Ucp1</i> mRNA expression in visceral WAT with no change in <i>Pgc1a</i>, <i>Lpl</i>, or <i>Hsl</i>. Expression of <i>Per1</i>, <i>Per2</i>, and <i>Nr1d1</i> mRNA in visceral WAT differed between long and short photoperiods over time when aligned to circadian time but not onset of darkness, indicating alterations in clock gene expression with photoperiod. These findings suggest that extended photoperiod through artificial light can promote visceral fat accumulation alone, independent of temperature, supporting that artificial light may play a role in obesity.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effects of Rat Bone Marrow Mesenchymal Stem Cells-Derived Fusogenic Plasma Membrane Vesicles Containing VSVG Protein Mediated Mitochondrial Transfer on Myocardial Injury In Vitro","authors":"Xin Liu,&nbsp;Hong Bian,&nbsp;Tingyuan Zhou,&nbsp;Chunjuan Zhao","doi":"10.1096/fba.2024-00235","DOIUrl":"https://doi.org/10.1096/fba.2024-00235","url":null,"abstract":"<p>Overexpression of spike glycoprotein G of vesicular stomatitis virus (VSVG) can induce the release of fusogenic plasma membrane vesicles (fPMVs), which can transport cytoplasmic, nuclear, and surface proteins directly to target cells. This study aimed to investigate the roles of rat bone marrow mesenchymal stem cells (rBMSCs)-derived fPMVs containing VSVG protein in myocardial injury and their related mechanisms. The plasmids of pLP-VSVG were used to transfect rBMSCs, and then fPMVs were obtained by mechanical extrusion. After that, H9c2 cells were first treated with hypoxia reoxygenation (HR) to establish a cardiomyocyte injury model, and then were treated with fPMVs to evaluate the rescue of rBMSCs-derived fPMVs on HR-induced cardiomyocyte injury. FPMVs containing VSVG protein were successfully prepared from rBMSCs with VSVG overexpression. Compared with control fPMVs, <i>ACTB</i>, <i>HDAC1</i>, VSVG, CD81, MTCO1, and TOMM20 were significantly up-regulated (<i>p</i> &lt; 0.05), while eEF2 was significantly down-regulated (<i>p</i> &lt; 0.05) in the fPMVs containing VSVG protein. Additionally, it was obvious fPMVs could carry mitochondria into H9c2 cells, and HR treatment significantly inhibited viability and induced apoptosis of H9c2 cells, as well as significantly increased the contents of TNF-α and IL-1β, and ROS levels both in cells and cellular mitochondria, while evidently reducing the levels of ATP, MRCC IV, and <i>MT-ND1</i> (<i>p</i> &lt; 0.05). However, fPVMs could remarkably reverse the changes in these indexes caused by HR (<i>p</i> &lt; 0.05). RBMSCs-derived fPMVs containing VSVG protein may have protective effects on myocardial injury by mediating mitochondrial transfer and regulating mitochondrial functions.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ogerin induced activation of Gpr68 alters tendon healing","authors":"Andrew Rodenhouse,&nbsp;Gilbert Smolyak,&nbsp;Emmanuela Adjei-Sowah,&nbsp;Neeta Adhikari,&nbsp;Samantha Muscat,&nbsp;Takuma Okutani,&nbsp;Constantinos Ketonis,&nbsp;Anne E. C. Nichols,&nbsp;Robert M. Kottmann,&nbsp;Alayna E. Loiselle","doi":"10.1096/fba.2024-00236","DOIUrl":"https://doi.org/10.1096/fba.2024-00236","url":null,"abstract":"<p>Satisfactory outcomes after acute tendon injuries are hampered by a fibrotic healing response. As such, modulation of extracellular matrix deposition and remodeling represents an important intervention point to improve healing. During fibrosis, matrix is deposited and remodeled by activated fibroblasts and/or myofibroblasts. Recent work has demonstrated that Ogerin, a positive allosteric modulator of the orphan proton-sensing GPCR, GPR68, can modulate fibroblast ↔ myofibroblast dynamics in multiple fibroblast populations, including blunting myofibroblast differentiation and facilitating reversion of mature myofibroblasts to a basal fibroblast state in vitro. In the present study, we tested the ability of Ogerin to modulate tendon fibroblast ↔ myofibroblast behavior in vitro and in vivo. Consistent with prior work, Ogerin can both blunt TGF-β induced tenocyte → myofibroblast differentiation and partially revert mature myofibroblasts to a basal tenocyte state. However, Ogerin treatment from days 8–12 after tendon repair surgery did not inhibit myofibroblast differentiation, and Ogerin treatment from post-operative days 24–28 did not induce myofibroblast reversion. Moreover, while we expected Ogerin treatment from days 8–12 to impair healing due to blunted extracellular matrix formation, Ogerin treatment improved tendon mechanical properties and altered cell transcriptional profiles and communication patterns in a way that suggests accelerated remodeling and resolution of the repair response, identifying Ogerin as a novel therapeutic approach to improve the tendon healing process.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Furin inhibits HSCs activation and ameliorates liver fibrosis by regulating PTEN-L/PINK1/parkin mediated mitophagy in mouse","authors":"Yan-Wei Song,&nbsp;Yu-Hua Zhu,&nbsp;Ming-Ze Ma","doi":"10.1096/fba.2024-00221","DOIUrl":"https://doi.org/10.1096/fba.2024-00221","url":null,"abstract":"<p>Hepatic Stellate cells (HSCs) play an important role during liver fibrosis progression; more and more evidence indicates that mitophagy greatly regulates HSCs activation. HSCs mitophagy mainly depends on the classical PINK1/Parkin pathway, which can be strongly regulated by phosphatase PTEN-long (PTEN-L). PTEN-L can be cleaved by Furin that leading to functional changes in the tumor regulation process. However, the impact of the interaction between Furin and PTEN-L on HSCs mitophagy remains unclear. Therefore, this study aims to explore the role of Furin in HSCs activation and liver fibrosis and its potential mechanisms. Our results revealed that Furin expression was obviously up-regulated during HSCs activation and mice liver fibrogenesis. We also found that the activation of primary HSCs can be inhibited by Furin treatment in vitro. Besides, functional studies showed that LX-2 cell proliferation and migration were obviously inhibited by Furin treatment. Further studies showed that mitochondrial membrane potential (MMP) was significantly reduced by Furin treatment, and the knockdown of PTEN-L expression caused similar effects. These results demonstrated the role of Furin in promoting HSCs mitophagy but leading to inhibition of HSCs persistent activation. Furthermore, we constructed a liver fibrosis mouse model by CCl4-induced method and found that forced expression of Furin caused alleviation of liver fibrosis in CCl4-induced mice. Our findings provide a new clue for understanding liver fibrogenesis and highlight the therapeutic potential of Furin for hepatic fibrosis.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00221","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Global warming and obesity: External heat exposure as a modulator of energy balance","authors":"Imani Muhammad,&nbsp;Francene Steinberg,&nbsp;Jennifer Larsen,&nbsp;Robert B. Rucker","doi":"10.1096/fba.2024-00140","DOIUrl":"https://doi.org/10.1096/fba.2024-00140","url":null,"abstract":"<p>In obesity research, the importance of core body temperature (CBT) regulation is often neglected. CBT thermogenic regulation, however, plays a crucial role in heat management through convection, radiation, and conduction processes to remove heat from the body, as well as metabolic processes that sequester heat through lipogenesis. This review emphasizes that even small changes in CBT can significantly impact metabolic events ranging from ATP production to fat deposition. Accordingly, a case is made that physical events, such as external heat exposure, also impact body compositional changes, as do work and metabolic processes. Examples are provided that suggest that independent diet and exercise, where one lives, can have an impact on body composition and obesity. For example, below 35 degrees of the earth's latitude, obesity rates are often 40 percent or greater among adults. However, in regions between 45 and 50 degrees latitude, such as the US-Canadian border, obesity rates are 25%–30%.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00140","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative analysis of dietary iron deprivation and supplementation in a murine model of colitis","authors":"Thanina Medjbeur,&nbsp;Ugo Sardo,&nbsp;Prunelle Perrier,&nbsp;Kevin Cormier,&nbsp;Maryline Roy,&nbsp;Anne Dumay,&nbsp;Léon Kautz","doi":"10.1096/fba.2025-00022","DOIUrl":"https://doi.org/10.1096/fba.2025-00022","url":null,"abstract":"<p>Inflammatory bowel diseases are chronic inflammatory conditions with growing prevalence in western populations. Iron is an essential component of erythrocytes hemoglobin. Under the influence of elevated hepcidin production, iron is sequestered in cells during inflammation which, in turn, leads to iron restriction for red blood cell synthesis. As a consequence, iron deficiency and anemia of inflammation are the most prevalent extraintestinal complications in IBD patients. Iron deficiency is commonly treated with oral iron supplements, with limited efficacy as iron absorption is blunted during intestinal inflammation. Moreover, iron supplementation can cause intestinal complications, as previous studies have shown that it can worsen the inflammatory response. However, a comparative analysis of the effects of low, adequate, and high dietary iron content matching the iron supplementation given to patients has not been performed in mice. We therefore tested the impact of dietary iron deprivation and supplementation in a murine model of colitis induced by dextran sodium sulfate. We found that both dietary iron deprivation and supplementation were accompanied by a more severe inflammation with earlier signs of gastrointestinal bleeding compared to mice fed an iron-adequate diet. The manipulation of dietary iron led to a profound dysbiosis in the colon of control mice that differed depending on the dietary iron content. Analysis of this dysbiosis is in line with a pronounced susceptibility to colonic inflammation, thus questioning the benefit/risk balance of oral iron supplementation for IBD patients.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 5","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2025-00022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrochlorothiazide combined with exercise training attenuates blood pressure variability and renal dysfunctions in an experimental model of hypertension and ovarian hormone deprivation","authors":"Pietra Petrica Neves,&nbsp;Maycon Junior Ferreira,&nbsp;Tânia Plens Shecaira,&nbsp;Marina Rascio Henriques Dutra,&nbsp;Débora Conte Kimura,&nbsp;Guiomar Nascimento Gomes,&nbsp;Kátia De Angelis","doi":"10.1096/fba.2024-00168","DOIUrl":"https://doi.org/10.1096/fba.2024-00168","url":null,"abstract":"<p>Considering that blood pressure variability (BPV) has been associated with damage to target organs such as the kidneys, this study aimed to investigate the effects of the association of hydrochlorothiazide (HCTZ) combined with exercise training (CET) on BPV, as well as morphology, function, inflammation, and oxidative stress in renal tissue. Our study was designed to experimentally simulate arterial hypertension associated with the postmenopausal period in females, a condition linked to a considerable increase in cardiovascular risk. To replicate the physiological cessation of ovarian hormones, we performed a bilateral ovariectomy. Female spontaneously hypertensive rats (SHR) were distributed into 4 ovariectomized groups (<i>n</i> = 5–6/group): sedentary (OS), sedentary + HCTZ (OSH), trained (OT), and trained + HCTZ (OTH). Both HCTZ (3 mg/kg) and CET (3 days/week) were performed for 8 weeks. Blood pressure (BP) was directly recorded for BPV analyses. Renal function, morphology, inflammation, and oxidative stress were evaluated. The OSH, OT, and OTH groups had lower systolic BP (SBP) (OSH: 189 ± 13; OT: 179 ± 5; OTH: 174 ± 15 mmHg) when compared to the OS group (208 ± 15 mmHg). Only the association of the drug with CET promoted a reduction in variance of SBP. The groups treated with HCTZ showed lower plasma creatinine levels and increased creatinine clearance compared to the OS group. Treated groups showed a reduction in fields of 51%–100% of interstitial tubule fibrosis when compared to the OS group, and the OTH group also showed reduction in fields in the range of 26%–50% versus other groups. There was an increase in renal catalase, a reduction in IL-6, and an increase in IL-10 in the OTH group. Positive correlations were obtained between variance of SBP and SBP (<i>r</i> = 0.72), plasma creatinine (<i>r</i> = 0.58), IL-6 (<i>r</i> = 0.62), hydrogen peroxide (<i>r</i> = 0.61), and protein oxidation (<i>r</i> = 0.66), as well as between vascular sympathetic modulation and lipoperoxidation (<i>r</i> = 0.62) in kidney tissue. In conclusion, our findings highlight the enhanced effectiveness of combining HCTZ and CET compared to using the drug alone in the studied model. This dual approach may provide additional cardiovascular and renal benefits beyond reduction of BP, potentially leading to improved quality of life and reduced morbidity associated with systemic arterial hypertension.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00168","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Holistic precision wellness: Paving the way for next-generation precision medicine (ngPM) with AI, biomedical informatics, and clinical medicine","authors":"Sawsan G. A. A. Mohammed,&nbsp;M. Walid Qoronfleh,&nbsp;Ahmet Acar,&nbsp;Nader I. Al-Dewik","doi":"10.1096/fba.2024-00198","DOIUrl":"https://doi.org/10.1096/fba.2024-00198","url":null,"abstract":"<p>A “quiet revolution” in medicine has been taking place over the past two decades. There are two converging dynamic forces that have propelled precision medicine to the limelight, garnering wide public attention. The first driver is the realization that populations within a disease area can be stratified, thus developing therapies tailored to their specific needs, and the capability to identify these populations by analyzing large, diverse datasets. The second driver is technology advances in multi-omics approaches and applications (i.e., molecularly informed medicine) enabling a more comprehensive portrait of disease biology. This promises to not only accelerate the development of precision medicine processes but also presents challenges for healthcare professionals and health systems that are struggling to interconnect and integrate disparate data sources into a cohesive clinical strategy to the benefit of their patients. We coin here the term next-generation precision medicine (ngPM), which is bound to become conventional in the clinics sooner or later. Artificial intelligence (AI) and machine learning (ML) in healthcare have transformative potential and are a strategic response to today's challenges and tomorrow's opportunities. The chief challenges here are how well precision medicine (PM) permeates primary care to become a standard of care and drive toward precision wellness or precision lifestyle (ngPM), while ensuring access to care is feasible, streamlined, and routine. We present here a perspective that would harness the power of ngPM for precision wellness.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00198","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of the Rbfox3-IRES-iCre knock-in mouse: Revealing gene recombination activity in neural and non-neural peripheral tissues","authors":"Shiho Nishino,&nbsp;Misuzu Hashimoto,&nbsp;Swapna Paramanya Biswas,&nbsp;Natsuki Mikami,&nbsp;Yoshikazu Hasegawa,&nbsp;Hayate Suzuki,&nbsp;Woojin Kang,&nbsp;Seiya Mizuno,&nbsp;Kazuya Murata","doi":"10.1096/fba.2024-00143","DOIUrl":"https://doi.org/10.1096/fba.2024-00143","url":null,"abstract":"<p>In vivo cell type-specific genetic recombination based on the Cre-loxP system has contributed to the understanding of biological processes and diseases. Neuronal nuclei (NeuN)/RBFOX3 is a widely used mature neuron marker in developmental biology and neuroscience. Here, we generated <i>Rbfox3</i>-improved Cre (iCre) knock-in mouse model and investigated the effect of iCre knock-in into the <i>Rbfox3</i> gene and Cre recombination activity in the central nervous system (CNS) and peripheral tissues. The knock-in of internal ribosome entry site (IRES)-iCre cassette into the <i>Rbfox3</i> 3′ UTR did not affect birth rate, growth, and brain weight. In the adult brain, iCre protein expression was confirmed, whereas RBFOX3 protein expression was partially reduced in the knock-in mice. Cre recombination analysis using R26GRR fluorescent reporter strain revealed that <i>Rbfox3</i>-driven iCre-induced gene recombination in the CNS and heart during embryonic development. In the adult brain, gene recombination was observed in neurons, however, not in other glial cells. In the peripheral tissues, iCre activity was found in the sciatic nerve and in other peripheral tissues, including the heart, bladder, and testis. We validated gene recombination rate in the germline and found that 100% recombination occurred in male germ cells and approximately 50% in female germ cells. Concludingly, <i>Rbfox3</i>-iCre mice induce genetic recombination in neurons within CNS as well as in some peripheral tissues and germ cells. In addition to establishing a novel Cre mouse line, the findings of this study offer valuable insights into the development and application of mouse tools that utilize the <i>Rbfox3</i> gene locus.</p>","PeriodicalId":12093,"journal":{"name":"FASEB bioAdvances","volume":"7 4","pages":""},"PeriodicalIF":2.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1096/fba.2024-00143","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143809863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}