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Kamiya A, Ida K. Liver Injury and Cell Survival in Non-Alcoholic Steatohepatitis Regulated by Sex-Based Difference through B Cell Lymphoma 6. Cells 2022; 11:cells11233751. [PMID: 36497010 PMCID: PMC9737870 DOI: 10.3390/cells11233751] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/14/2022] [Accepted: 11/20/2022] [Indexed: 11/25/2022] Open
Abstract
The liver is a crucial organ for maintaining homeostasis in living organisms and is the center of various metabolic functions. Therefore, abnormal metabolic activity, as in metabolic syndrome, leads to pathological conditions, such as abnormal accumulation of lipids in the liver. Inflammation and cell death are induced by several stresses in the fatty liver, namely steatohepatitis. In recent years, an increase in non-alcoholic steatohepatitis (NASH), which is not dependent on excessive alcohol intake, has become an issue as a major cause of liver cirrhosis and liver cancer. There are several recent findings on functional sex-based differences, NASH, and cell stress and death in the liver. In particular, NASH-induced liver injury and tumorigeneses were suppressed by B cell lymphoma 6, the transcriptional factor regulating sex-based liver functional gene expression. In this review, we discuss cell response to stress and lipotoxicity in NASH and its regulatory mechanisms.
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Affiliation(s)
- Akihide Kamiya
- Correspondence: ; Tel.: +81-463-93-1121 (ext. 2783); Fax: +81-463-95-3522
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Li M, Zhou X, Wang W, Ji B, Shao Y, Du Q, Yao J, Yang Y. Selecting an Appropriate Experimental Animal Model for Cholangiocarcinoma Research. J Clin Transl Hepatol 2022; 10:700-710. [PMID: 36062286 PMCID: PMC9396327 DOI: 10.14218/jcth.2021.00374] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2021] [Revised: 12/05/2021] [Accepted: 01/03/2022] [Indexed: 12/04/2022] Open
Abstract
Cholangiocarcinoma (CCA) is a highly aggressive biliary tree malignancy with intrahepatic and extra-hepatic subtypes that differ in molecular pathogeneses, epidemiology, clinical manifestations, treatment, and prognosis. The overall prognosis and patient survival remains poor because of lack of early diagnosis and effective treatments. Preclinical in vivo studies have become increasingly paramount as they are helpful not only for the study of the fundamental molecular mechanisms of CCA but also for developing novel and effective therapeutic approaches of this fatal cancer. Recent advancements in cell and molecular biology have made it possible to mimic the pathogenicity of human CCA in chemical-mechanical, infection-induced inflammatory, implantation, and genetically engineered animal models. This review is intended to help investigators understand the particular strengths and weaknesses of the currently used in vivo animal models of human CCA and their related modeling techniques to aid in the selection of the one that is the best for their research needs.
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Affiliation(s)
- Man Li
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Xueli Zhou
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Wei Wang
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Baoan Ji
- Department of Cancer Biology, Mayo Clinic, Jacksonville, Florida, USA
| | - Yu Shao
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Qianyu Du
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Jinghao Yao
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
| | - Yan Yang
- Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, China
- Correspondence to: Yan Yang, Department of Medical Oncology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China. ORCID: https://orcid.org/0000-0003-0887-2770. Tel: +86-552-3086178, Fax: +86-552-3074480, E-mail:
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3
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Muto Y, Moroishi T, Ichihara K, Nishiyama M, Shimizu H, Eguchi H, Moriya K, Koike K, Mimori K, Mori M, Katayama Y, Nakayama KI. Disruption of FBXL5-mediated cellular iron homeostasis promotes liver carcinogenesis. J Exp Med 2019; 216:950-965. [PMID: 30877170 PMCID: PMC6446870 DOI: 10.1084/jem.20180900] [Citation(s) in RCA: 43] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 01/15/2019] [Accepted: 02/25/2019] [Indexed: 12/17/2022] Open
Abstract
Hepatocellular iron overload elicited by ablation of the iron-sensing ubiquitin ligase FBXL5 promotes liver carcinogenesis induced by exposure to a chemical carcinogen or hepatitis virus, suggesting that FBXL5 is a previously unrecognized oncosuppressor in liver carcinogenesis in mice. Hepatic iron overload is a risk factor for progression of hepatocellular carcinoma (HCC), although the molecular mechanisms underlying this association have remained unclear. We now show that the iron-sensing ubiquitin ligase FBXL5 is a previously unrecognized oncosuppressor in liver carcinogenesis in mice. Hepatocellular iron overload elicited by FBXL5 ablation gave rise to oxidative stress, tissue damage, inflammation, and compensatory proliferation of hepatocytes and to consequent promotion of liver carcinogenesis induced by exposure to a chemical carcinogen. The tumor-promoting outcome of FBXL5 deficiency in the liver was also found to be effective in a model of virus-induced HCC. FBXL5-deficient mice thus constitute the first genetically engineered mouse model of liver carcinogenesis promoted by iron overload. In addition, dysregulation of FBXL5-mediated cellular iron homeostasis was found to be associated with poor prognosis in human HCC, suggesting that FBXL5 plays a key role in defense against hepatocarcinogenesis.
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Affiliation(s)
- Yoshiharu Muto
- Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
| | - Toshiro Moroishi
- Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
| | - Kazuya Ichihara
- Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
| | - Masaaki Nishiyama
- Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
| | - Hideyuki Shimizu
- Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Kyoji Moriya
- Department of Infection Control and Prevention, The University of Tokyo Hospital, Tokyo, Japan
| | - Kazuhiko Koike
- Department of Gastroenterology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Koshi Mimori
- Department of Surgery, Kyushu University, Beppu Hospital, Beppu, Japan
| | - Masaki Mori
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Japan
| | - Yuta Katayama
- Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
| | - Keiichi I Nakayama
- Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan
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Benhamouche-Trouillet S, O'Loughlin E, Liu CH, Polacheck W, Fitamant J, McKee M, El-Bardeesy N, Chen CS, McClatchey AI. Proliferation-independent role of NF2 (merlin) in limiting biliary morphogenesis. Development 2018; 145:dev162123. [PMID: 29712669 PMCID: PMC10682933 DOI: 10.1242/dev.162123] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2017] [Accepted: 04/03/2018] [Indexed: 12/15/2022]
Abstract
The architecture of individual cells and cell collectives enables functional specification, a prominent example being the formation of epithelial tubes that transport fluid or gas in many organs. The intrahepatic bile ducts (IHBDs) form a tubular network within the liver parenchyma that transports bile to the intestine. Aberrant biliary 'neoductulogenesis' is also a feature of several liver pathologies including tumorigenesis. However, the mechanism of biliary tube morphogenesis in development or disease is not known. Elimination of the neurofibromatosis type 2 protein (NF2; also known as merlin or neurofibromin 2) causes hepatomegaly due to massive biliary neoductulogenesis in the mouse liver. We show that this phenotype reflects unlimited biliary morphogenesis rather than proliferative expansion. Our studies suggest that NF2 normally limits biliary morphogenesis by coordinating lumen expansion and cell architecture. This work provides fundamental insight into how biliary fate and tubulogenesis are coordinated during development and will guide analyses of disease-associated and experimentally induced biliary pathologies.
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Affiliation(s)
- Samira Benhamouche-Trouillet
- Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA
- Harvard Medical School, Boston, MA 02114, USA
- Molecular Pathology, Massachusetts General Hospital, Charlestown, MA 02129, USA
| | - Evan O'Loughlin
- Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA
- Harvard Medical School, Boston, MA 02114, USA
- Molecular Pathology, Massachusetts General Hospital, Charlestown, MA 02129, USA
| | - Ching-Hui Liu
- Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA
- Harvard Medical School, Boston, MA 02114, USA
- Molecular Pathology, Massachusetts General Hospital, Charlestown, MA 02129, USA
| | - William Polacheck
- Department of Biomedical Engineering, Boston University, Wyss Institute, Boston, MA 02115, USA
| | - Julien Fitamant
- Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA
| | - Mary McKee
- Center for Systems Biology, Program in Membrane Biology, Division of Nephrology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston MA 02114, USA
| | - Nabeel El-Bardeesy
- Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA
| | - Christopher S Chen
- Department of Biomedical Engineering, Boston University, Wyss Institute, Boston, MA 02115, USA
| | - Andrea I McClatchey
- Massachusetts General Hospital Cancer Center, Charlestown, MA 02129, USA
- Harvard Medical School, Boston, MA 02114, USA
- Molecular Pathology, Massachusetts General Hospital, Charlestown, MA 02129, USA
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Schatton D, Pla-Martin D, Marx MC, Hansen H, Mourier A, Nemazanyy I, Pessia A, Zentis P, Corona T, Kondylis V, Barth E, Schauss AC, Velagapudi V, Rugarli EI. CLUH regulates mitochondrial metabolism by controlling translation and decay of target mRNAs. J Cell Biol 2017; 216:675-693. [PMID: 28188211 PMCID: PMC5350512 DOI: 10.1083/jcb.201607019] [Citation(s) in RCA: 60] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 12/06/2016] [Accepted: 01/06/2017] [Indexed: 12/21/2022] Open
Abstract
Mitochondria are essential organelles that host crucial metabolic pathways and produce adenosine triphosphate. The mitochondrial proteome is heterogeneous among tissues and can dynamically change in response to different metabolic conditions. Although the transcriptional programs that govern mitochondrial biogenesis and respiratory function are well known, posttranscriptional regulatory mechanisms remain unclear. In this study, we show that the cytosolic RNA-binding protein clustered mitochondria homologue (CLUH) regulates the expression of a mitochondrial protein network supporting key metabolic programs required under nutrient deprivation. CLUH exerts its function by controlling the stability and translation of target messenger RNAs. In the absence of Cluh, mitochondria are severely depleted of crucial enzymes involved in catabolic energy-converting pathways. CLUH preserves oxidative mitochondrial function and glucose homeostasis, thus preventing death at the fetal-neonatal transition. In the adult liver, CLUH ensures maximal respiration capacity and the metabolic response to starvation. Our results shed new light on the posttranscriptional mechanisms controlling the expression of mitochondrial proteins and suggest novel strategies to tailor mitochondrial function to physiological and pathological conditions.
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Affiliation(s)
- Désirée Schatton
- Institute for Genetics, University of Cologne, 50674 Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany
| | - David Pla-Martin
- Institute for Genetics, University of Cologne, 50674 Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany
| | - Marie-Charlotte Marx
- Institute for Genetics, University of Cologne, 50674 Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany
| | - Henriette Hansen
- Institute for Genetics, University of Cologne, 50674 Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany
| | - Arnaud Mourier
- Department of Mitochondrial Biology, Max Planck Institute for Biology of Ageing, 50931 Cologne, Germany
| | - Ivan Nemazanyy
- Paris Descartes University, Sorbonne Paris Cité, 75006 Paris, France
| | - Alberto Pessia
- Metabolomics Unit, Institute for Molecular Medicine Finland, University of Helsinki, 00290 Helsinki, Finland
| | - Peter Zentis
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany
| | - Teresa Corona
- Institute for Genetics, University of Cologne, 50674 Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany
| | - Vangelis Kondylis
- Institute for Genetics, University of Cologne, 50674 Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany
| | - Esther Barth
- Institute for Genetics, University of Cologne, 50674 Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany
| | - Astrid C Schauss
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany
| | - Vidya Velagapudi
- Metabolomics Unit, Institute for Molecular Medicine Finland, University of Helsinki, 00290 Helsinki, Finland
| | - Elena I Rugarli
- Institute for Genetics, University of Cologne, 50674 Cologne, Germany
- Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, 50931 Cologne, Germany
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Chiasson-MacKenzie C, Morris ZS, Baca Q, Morris B, Coker JK, Mirchev R, Jensen AE, Carey T, Stott SL, Golan DE, McClatchey AI. NF2/Merlin mediates contact-dependent inhibition of EGFR mobility and internalization via cortical actomyosin. J Cell Biol 2015; 211:391-405. [PMID: 26483553 PMCID: PMC4621825 DOI: 10.1083/jcb.201503081] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2015] [Accepted: 09/01/2015] [Indexed: 01/04/2023] Open
Abstract
Merlin and Ezrin are central to a mechanism whereby mechanical forces transduced across the apical actomyosin cytoskeleton from cell junctions control the mobility and internalization of EGFR, providing novel insight into how cells inhibit mitogenic signaling in response to cell contact. The proliferation of normal cells is inhibited at confluence, but the molecular basis of this phenomenon, known as contact-dependent inhibition of proliferation, is unclear. We previously identified the neurofibromatosis type 2 (NF2) tumor suppressor Merlin as a critical mediator of contact-dependent inhibition of proliferation and specifically found that Merlin inhibits the internalization of, and signaling from, the epidermal growth factor receptor (EGFR) in response to cell contact. Merlin is closely related to the membrane–cytoskeleton linking proteins Ezrin, Radixin, and Moesin, and localization of Merlin to the cortical cytoskeleton is required for contact-dependent regulation of EGFR. We show that Merlin and Ezrin are essential components of a mechanism whereby mechanical forces associated with the establishment of cell–cell junctions are transduced across the cell cortex via the cortical actomyosin cytoskeleton to control the lateral mobility and activity of EGFR, providing novel insight into how cells inhibit mitogenic signaling in response to cell contact.
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Affiliation(s)
- Christine Chiasson-MacKenzie
- Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129 Department of Pathology, Massachusetts General Hospital, Charlestown, MA 02129 Department of Pathology, Harvard Medical School, Boston, MA 02115
| | - Zachary S Morris
- Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129 Department of Pathology, Massachusetts General Hospital, Charlestown, MA 02129 Department of Pathology, Harvard Medical School, Boston, MA 02115
| | - Quentin Baca
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115
| | - Brett Morris
- Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129 Department of Pathology, Massachusetts General Hospital, Charlestown, MA 02129 Department of Pathology, Harvard Medical School, Boston, MA 02115
| | - Joanna K Coker
- Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129 Department of Pathology, Massachusetts General Hospital, Charlestown, MA 02129 Department of Pathology, Harvard Medical School, Boston, MA 02115
| | - Rossen Mirchev
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115
| | - Anne E Jensen
- Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129 BioMEMs Resource Center, Massachusetts General Hospital, Charlestown, MA 02129
| | - Thomas Carey
- Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129 BioMEMs Resource Center, Massachusetts General Hospital, Charlestown, MA 02129
| | - Shannon L Stott
- Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129 BioMEMs Resource Center, Massachusetts General Hospital, Charlestown, MA 02129 Department of Medicine, Harvard Medical School, Boston, MA 02115
| | - David E Golan
- Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115
| | - Andrea I McClatchey
- Center for Cancer Research, Massachusetts General Hospital, Charlestown, MA 02129 Department of Pathology, Massachusetts General Hospital, Charlestown, MA 02129 Department of Pathology, Harvard Medical School, Boston, MA 02115
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Dou Z, Chattopadhyay M, Pan JA, Guerriero JL, Jiang YP, Ballou LM, Yue Z, Lin RZ, Zong WX. The class IA phosphatidylinositol 3-kinase p110-beta subunit is a positive regulator of autophagy. ACTA ACUST UNITED AC 2010; 191:827-43. [PMID: 21059846 PMCID: PMC2983054 DOI: 10.1083/jcb.201006056] [Citation(s) in RCA: 74] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
p110-β associates with the Vps34–Vps15–Beclin 1–Atg14L complex and facilitates generation of PtdIns(3)P to promote autophagy. Autophagy is an evolutionarily conserved cell renewal process that depends on phosphatidylinositol 3-phosphate (PtdIns(3)P). In metazoans, autophagy is inhibited by PtdIns(3,4,5)P3, the product of class IA PI3Ks, which mediates the activation of the Akt–TOR kinase cascade. However, the precise function of class IA PI3Ks in autophagy remains undetermined. Class IA PI3Ks are heterodimeric proteins consisting of an 85-kD regulatory subunit and a 110-kD catalytic subunit. Here we show that the class IA p110-β catalytic subunit is a positive regulator of autophagy. Genetic deletion of p110-β results in impaired autophagy in mouse embryonic fibroblasts, liver, and heart. p110-β does not promote autophagy by affecting the Akt–TOR pathway. Rather, it associates with the autophagy-promoting Vps34–Vps15–Beclin 1–Atg14L complex and facilitates the generation of cellular PtdIns(3)P. Our results unveil a previously unknown function for p110-β as a positive regulator of autophagy in multicellular organisms.
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Affiliation(s)
- Zhixun Dou
- Department of Molecular Genetics & Microbiology, Stony Brook University, Stony Brook, NY 11794, USA
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Zhu HZ, Chen JQ, Cheng GX, Xue JL. Generation and characterization of transgenic mice expressing tamoxifen-inducible cre-fusion protein specifically in mouse liver. World J Gastroenterol 2003; 9:1844-7. [PMID: 12918135 PMCID: PMC4611558 DOI: 10.3748/wjg.v9.i8.1844] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To establish transgenic mice expressing tamoxifen-inducible Cre-ERt recombinase specifically in the liver and to provide an efficient animal model for studying gene function in the liver and creating various mouse models mimicking human diseases.
METHODS: Alb-Cre-ERt transgenic mice were produced by microinjecting the construct with Cre-ERt fusion gene of DNA fragments into fertilized eggs derived from inbred C57BL/6 strain. Transgenic mice were identified by using PCR and Southern blotting. Expression of Cre-ERt fusion gene was analyzed in the liver, kidney, brain and lung from F1 generation transgenic mice at 8 weeks of age by reverse transcription (RT)-PCR.
RESULTS: Four hundred and fourteen fertilized eggs of C57 BL/6 mice were microinjected with recombinant Alb-Cre-ERt DNA fragments, and 312 survival eggs injected were transferred to the oviducts of 12 pseudopregnant recipient mice, 6 of 12 recipient mice became pregnant and gave birth to 44 offsprings. Of the 44 offsprings, two males and one female carried the hybrid Cre-ERt fusion gene. Three mice were determined as founders, and were back crossed to set up F1 generations with other inbred C57BL/6 mice. Transmission of Cre-ERt fusion gene in F1 offspring followed Mendelian rules. The expression of Cre-ERt mRNA was detected only in the liver of F1 offspring from two of three founder mice.
CONCLUSION: Transgenic mice expressing tamoxifen-inducible Cre-ERt recombinase under control of the liver-specific promoter are preliminary established.
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Affiliation(s)
- Huan-Zhang Zhu
- Institute of Pathology, Southwest Hospital, Third Military Medical University, Chongqing, China
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