The TK-NOG humanized liver platform provides durable human hepatocyte engraftment for translational studies in metabolism, toxicity, infectious disease, and liver biology.
Researchers can access human hepatocyte-engrafted TK-NOG mice for in-house testing, or access integrated in vivo pharmacology services via TransCure bioServices to support liver-focused drug development.
Humanized liver mouse models enable the study of human liver biology within an in vivo system, providing a powerful translational bridge between in vitro systems and clinical research.
Taconic’s platform is built on the TK-NOG mouse, an immunodeficient strain engineered to support robust human hepatocyte engraftment following induced transient liver injury. After engraftment, human hepatocytes repopulate the mouse liver and establish functional human liver chimerism.
Unlike models requiring ongoing liver injury, the TK-NOG system enables stable engraftment that does not interfere with downstream studies, allowing investigators to evaluate pharmacology, metabolism, disease mechanisms, and host-pathogen interactions over extended study durations.
Taconic now combines its expertise in genetically engineered mouse models with TransCure bioServices’ in vivo pharmacology capabilities, providing researchers access to fully integrated humanized liver study support and execution.
Ganciclovir administration transiently injures mouse hepatocytes, opening a niche for human hepatocyte transplantation
Primary human hepatocytes are engrafted into the ganciclovir-primed liver
Human hepatocytes establish within the mouse liver providing a durable platform for drug discovery and development
The TK-NOG mouse enables efficient engraftment of primary human hepatocytes and supports durable human liver repopulation.
Available options for human hepatocyte-engrafted TK-NOG mice include:
Created in BioRender.com
Humanized liver mice are widely used to investigate human-specific liver biology and drug responses that cannot be modeled in conventional rodents or in vitro systems.
Engrafted hepatocytes express human drug-metabolizing enzymes, enabling evaluation of:
Humanized liver models allow researchers to assess human-relevant toxicity mechanisms, supporting early identification of potential safety issues.
Humanized liver mice are used to model human hepatotropic pathogens, including viral infections that require human hepatocytes for replications (e.g. HBV,HCV, HDV).
Humanized liver mice enable investigation of human hepatocyte responses to metabolic stress and injury, supporting translational studies of MASH, fatty liver disease, and liver fibrosis.
These models support investigation of human liver biology, regeneration, cell/gene therapies, and disease processes in an in vivo context.
The TK-NOG Humanized Liver Platform combines model reliability, translational relevance, and integrated study capabilities.
Following initial hepatocyte engraftment, the model supports stable human liver chimerism without continued or repeat/cycling liver damage, allowing normal physiology to be maintained during studies.
Human hepatocyte engraftment can remain stable for extended periods, enabling studies lasting up to one year.
Humanized liver TK-NOG mice are engrafted with primary human hepatocytes, enabling physiologically relevant liver function and human-specific metabolic activity. Through Taconic’s integration with TransCure bioServices, researchers benefit from TransCure’s access to high-quality primary human hepatocytes and their extensive experience in achieving robust liver engraftment. Additionally, researchers can provide their own hepatocytes for custom engraftment.
This expertise supports reliable human hepatocyte repopulation and consistent model performance, enhancing the translational relevance of studies involving drug metabolism, pharmacology, and liver biology.
The TK-NOG humanized liver model is supported by a strong body of published research and a long history of use in translational liver studies. The model was originally developed at the Central Institute for Experimental Medicine (CIEM), and Taconic maintains a longstanding partnership with CIEM to advance and refine the platform.
Through this collaboration, Taconic and TransCure bioServices continue to work with CIEM scientists to optimize the performance and reliability of humanized TK-NOG mice, ensuring researchers have access to a well-characterized model supported by ongoing scientific development.
The integration of Taconic’s model expertise with TransCure’s in vivo pharmacology services enables comprehensive study design, execution, and analysis.
Taconic’s humanized liver platform provides access to proven TK-NOG models and TransCure’s integrated in vivo study capabilities to support translational liver drug development.Whether you need engrafted or non-engrafted mice, custom engraftment, or full pharmacology studies, Taconic and TransCure can help design the right solution.
Researchers can leverage Taconic and TransCure’s scientific teams to design and execute custom studies using humanized liver mice.
Projects are supported by PhD-trained scientific specialists who help connect researchers with the most appropriate models and experimental strategies.
A humanized liver mouse is a mouse in which a portion of the liver has been repopulated with human hepatocytes. These human hepatocytes perform many of the metabolic and functional activities of human liver cells, enabling researchers to study human-specific liver biology, drug metabolism, and host-pathogen interactions in vivo.
The TK-NOG mouse is an immunodeficient mouse strain engineered to support efficient engraftment of primary human hepatocytes following transient liver injury induced by ganciclovir administration. The model carries a liver-specific thymidine kinase (TK) transgene, which enables controlled hepatocyte injury when the antiviral drug ganciclovir is administered.
Hepatocytes expressing the TK transgene intracellularly convert ganciclovir into the toxic metabolite ganciclovir monophosphate, resulting in selective liver injury that creates space for transplanted human hepatocytes to engraft and expand. Ganciclovir is used only to induce this transient injury prior to engraftment.
The model was originally developed at the Central Institute for Experimental Medicine (CIEM) and has been widely used in translational liver research. Taconic maintains a longstanding partnership with CIEM and continues collaborative work to further refine and improve the performance of the TK-NOG platform.
Liver humanization is achieved by transplanting primary human hepatocytes into TK-NOG mice following controlled liver injury. The transplanted human hepatocytes expand and repopulate the liver, creating a chimeric organ containing functional human liver cells.
The liver injury used to facilitate hepatocyte engraftment is transient and occurs prior to study initiation. Once human hepatocytes repopulate the liver, the injury mechanism is no longer active, allowing downstream studies to proceed without ongoing liver damage.
The TK-NOG model supports efficient engraftment and durable repopulation of primary human hepatocytes, enabling long-term studies of human liver function. Because the liver injury used to initiate engraftment is transient, the model does not involve ongoing injury following humanization. The TK-NOG platform also has a strong scientific track record and continues to be refined through collaboration between Taconic, TransCure and CIEM.
Human hepatocyte engraftment in TK-NOG mice is stable once liver repopulation is established. The resulting human liver chimerism can be maintained for extended periods (greater than one year), enabling longitudinal studies of liver biology and pharmacology.
Humanized liver TK-NOG mice can support extended study durations, with human hepatocyte engraftment remaining stable for the life of the mouse. In some cases, studies may be conducted for up to approximately one year following engraftment, depending on study design.
Human liver chimerism is indicated by a Replacement Index (RI) that is calculated as the percentage of liver area populated by human cells (using markers such as HLA or human albumin). By convention, successful engraftment is defined as a RI greater than 20%. This is roughly equivalent to circulating human albumin levels greater than 1 mg/mL.
Human liver chimerism is monitored using human albumin levels in serum, which correlate with the extent of human hepatocyte repopulation. As a general rule, circulating human albumin levels greater than 1 mg/mL indicates successful engraftment. Additional methods such as histological analysis or molecular assays may also be used to evaluate liver humanization post-mortem.
Human hepatocytes used for engraftment are obtained from qualified primary hepatocyte sources in line with applicable ethical and legal guidelines. Through Taconic’s integration with TransCure bioServices, researchers benefit from TransCure’s access to high-quality primary human hepatocytes and extensive experience in achieving robust human liver engraftment.
Yes. Human hepatocyte donors can be pre-screened for specific characteristics when required for a study via TransCure. This may include factors such as HLA type or other donor attributes (e.g. specific alleles, gene mutations, copy number variations), depending on research objectives.
TransCure scientists can work with investigators to determine whether donor pre-screening or selection criteria are appropriate for a given study and help coordinate hepatocyte sourcing.
Yes. Different hepatocyte donors may be used depending on study objective, such as evaluating donor-specific metabolic profiles or investigating variability in drug metabolism or other functional readouts.
Yes. Double-humanized mouse models combining human hepatocytes and a human immune system can be generated when required for specific research applications.
Researchers can access TK-NOG models engrafted with human cord blood-derived CD34+ hematopoietic stem cells to generate a humanized immune system alongside human hepatocyte engraftment in the liver. These models may be useful for studies investigating interactions between human liver biology, immune function, and infectious disease.
Taconic Scientific Solutions Consultants can help determine whether a dual-humanized approach is appropriate for a given study.
Humanized liver TK-NOG mice are used in a range of research areas, including:
Yes. Taconic, together with TransCure bioServices, a Taconic Biosciences Company, offers integrated in vivo pharmacology study capabilities using humanized liver models. Scientific teams can assist with study design, execution, and data analysis.
Yes. Humanized liver TK-NOG mice can be shipped to qualified research facilities or contract research organizations, subject to applicable regulatory requirements. Shipping is currently available only within the EU.
Humanized liver TK-NOG mice are sold under label license subject to Conditions of Use. A separate license is not required and applicable licensing fees are included in the purchase price. Humanized liver TK-NOG mice may be used at your facility or a preferred CRO, subject to Conditions of Use. Shipping is currently available only within the EU.
Nonprofit users (excluding users at nonprofit foundations which are affiliated with a for-profit entity): For internal research purposes, the CIEA NOG mouse® Conditions of Use for nonprofit users apply. If you wish to perform sponsored research or fee-for-service contract research using the CIEA NOG mouse®, please inquire for access conditions.
For-profit users and users at foundations which are affiliated with for-profit entities: The CIEA NOG mouse® Conditions of Use for for-profit users apply.
No.
Researchers interested in humanized liver TK-NOG models can contact Taconic. Taconic Customer Relationship Managers and Scientific Solutions Consultants will help determine your research needs and connect you with TransCure’s Scientific team to discuss specific study objectives, model selection, and study design/execution.
1. Hasegawa M, Kawai K, Mitsui T, Taniguchi K, Monnai M, Wakui M, et al. The reconstituted 'humanized liver' in TK-NOG mice is mature and functional. Biochem Biophys Res Commun. 2011;405(3):405-10. https://doi.org/10.1016/j.bbrc.2011.01.042
2. Yamazaki H, Suemizu H, Shimizu M, Igaya S, Shibata N, Nakamura M, et al. In vivo formation of dihydroxylated and glutathione conjugate metabolites derived from thalidomide and 5-Hydroxythalidomide in humanized TK-NOG mice. Chem Res Toxicol. 2012;25(2):274-6. https://doi.org/10.1021/tx300009j
3. Grompe M, Strom S. Mice with human livers. Gastroenterology. 2013;145(6):1209-14. https://doi.org/10.1053/j.gastro.2013.09.009
4. Hu Y, Wu M, Nishimura T, Zheng M, Peltz G. Human pharmacogenetic analysis in chimeric mice with 'humanized livers'. Pharmacogenet Genomics. 2013;23(2):78-83. https://doi.org/10.1097/FPC.0b013e32835cb2c7
5. Kosaka K, Hiraga N, Imamura M, Yoshimi S, Murakami E, Nakahara T, et al. A novel TK-NOG based humanized mouse model for the study of HBV and HCV infections. Biochem Biophys Res Commun. 2013;441(1):230-5. https://doi.org/10.1016/j.bbrc.2013.10.040
6. Tsukada A, Suemizu H, Murayama N, Takano R, Shimizu M, Nakamura M, et al. Plasma concentrations of melengestrol acetate in humans extrapolated from the pharmacokinetics established in in vivo experiments with rats and chimeric mice with humanized liver and physiologically based pharmacokinetic modeling. Regul Toxicol Pharmacol. 2013;65(3):316-24. https://doi.org/10.1016/j.yrtph.2013.01.008
7. Yamazaki H, Suemizu H, Murayama N, Utoh M, Shibata N, Nakamura M, et al. In vivo drug interactions of the teratogen thalidomide with midazolam: heterotropic cooperativity of human cytochrome P450 in humanized TK-NOG mice. Chem Res Toxicol. 2013;26(3):486-9. https://doi.org/10.1021/tx400008g
8. Higuchi Y, Kawai K, Yamazaki H, Nakamura M, Bree F, Guguen-Guillouzo C, et al. The human hepatic cell line HepaRG as a possible cell source for the generation of humanized liver TK-NOG mice. Xenobiotica. 2014;44(2):146-53. https://doi.org/10.3109/00498254.2013.836257
9. Kim M, Choi B, Joo SY, Lee H, Lee JH, Lee KW, et al. Generation of humanized liver mouse model by transplant of patient-derived fresh human hepatocytes. Transplant Proc. 2014;46(4):1186-90. https://doi.org/10.1016/j.transproceed.2013.11.098
10. Xu D, Nishimura T, Nishimura S, Zhang H, Zheng M, Guo YY, et al. Fialuridine induces acute liver failure in chimeric TK-NOG mice: a model for detecting hepatic drug toxicity prior to human testing. PLoS Med. 2014;11(4):e1001628. https://doi.org/10.1371/journal.pmed.1001628
11. Kai Y, Hikita H, Tatsumi T, Nakabori T, Saito Y, Morishita N, et al. Emergence of hepatitis C virus NS5A L31V plus Y93H variant upon treatment failure of daclatasvir and asunaprevir is relatively resistant to ledipasvir and NS5B polymerase nucleotide inhibitor GS-558093 in human hepatocyte chimeric mice. J Gastroenterol. 2015;50(11):1145-51. https://doi.org/10.1007/s00535-015-1108-6
12. Kamimura H, Ito S, Nozawa K, Nakamura S, Chijiwa H, Nagatsuka S, et al. Formation of the accumulative human metabolite and human-specific glutathione conjugate of diclofenac in TK-NOG chimeric mice with humanized livers. Drug Metab Dispos. 2015;43(3):309-16. https://doi.org/10.1124/dmd.114.061689
13. Nishiyama S, Suemizu H, Shibata N, Guengerich FP, Yamazaki H. Simulation of Human Plasma Concentrations of Thalidomide and Primary 5-Hydroxylated Metabolites Explored with Pharmacokinetic Data in Humanized TK-NOG Mice. Chem Res Toxicol. 2015;28(11):2088-90. https://doi.org/10.1021/acs.chemrestox.5b00381
14. Soulard V, Bosson-Vanga H, Lorthiois A, Roucher C, Franetich JF, Zanghi G, et al. Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice. Nat Commun. 2015;6:7690. https://doi.org/10.1038/ncomms8690
15. Uchida T, Hiraga N, Imamura M, Tsuge M, Abe H, Hayes CN, et al. Human Cytotoxic T Lymphocyte-Mediated Acute Liver Failure and Rescue by Immunoglobulin in Human Hepatocyte Transplant TK-NOG Mice. J Virol. 2015;89(19):10087-96. https://doi.org/10.1128/JVI.01126-15
16. Xu D, Michie SA, Zheng M, Takeda S, Wu M, Peltz G. Humanized thymidine kinase-NOG mice can be used to identify drugs that cause animal-specific hepatotoxicity: a case study with furosemide. J Pharmacol Exp Ther. 2015;354(1):73-8. https://doi.org/10.1124/jpet.115.224493
17. Xu D, Wu M, Nishimura S, Nishimura T, Michie SA, Zheng M, et al. Chimeric TK-NOG mice: a predictive model for cholestatic human liver toxicity. J Pharmacol Exp Ther. 2015;352(2):274-80. https://doi.org/10.1124/jpet.114.220798
18. Higuchi Y, Kawai K, Kanaki T, Yamazaki H, Chesne C, Guguen-Guillouzo C, et al. Functional polymer-dependent 3D culture accelerates the differentiation of HepaRG cells into mature hepatocytes. Hepatol Res. 2016;46(10):1045-57. https://doi.org/10.1111/hepr.12644
19. Nakabori T, Hikita H, Murai K, Nozaki Y, Kai Y, Makino Y, et al. Sodium taurocholate cotransporting polypeptide inhibition efficiently blocks hepatitis B virus spread in mice with a humanized liver. Sci Rep. 2016;6:27782. https://doi.org/10.1038/srep27782
20. Utoh M, Suemizu H, Mitsui M, Kawano M, Toda A, Uehara S, et al. Human plasma concentrations of cytochrome P450 probe cocktails extrapolated from pharmacokinetics in mice transplanted with human hepatocytes and from pharmacokinetics in common marmosets using physiologically based pharmacokinetic modeling. Xenobiotica. 2016;46(12):1049-55. https://doi.org/10.3109/00498254.2016.1147102
21. Fomin ME, Beyer AI, Muench MO. Human fetal liver cultures support multiple cell lineages that can engraft immunodeficient mice. Open Biol. 2017;7(12). https://doi.org/10.1098/rsob.170108
22. Kamimura H, Ito S, Chijiwa H, Okuzono T, Ishiguro T, Yamamoto Y, et al. Simulation of human plasma concentration-time profiles of the partial glucokinase activator PF-04937319 and its disproportionate N-demethylated metabolite using humanized chimeric mice and semi-physiological pharmacokinetic modeling. Xenobiotica. 2017;47(5):382-93. https://doi.org/10.1080/00498254.2016.1199063
23. Shimizu M, Suemizu H, Mitsui M, Shibata N, Guengerich FP, Yamazaki H. Metabolic profiles of pomalidomide in human plasma simulated with pharmacokinetic data in control and humanized-liver mice. Xenobiotica. 2017;47(10):844-8. https://doi.org/10.1080/00498254.2016.1247218
24. Suzuki E, Koyama K, Nakai D, Goda R, Kuga H, Chiba K. Observation of Clinically Relevant Drug Interaction in Chimeric Mice with Humanized Livers: The Case of Valproic Acid and Carbapenem Antibiotics. Eur J Drug Metab Pharmacokinet. 2017;42(6):965-72. https://doi.org/10.1007/s13318-017-0413-2
25. Dagur RS, Wang W, Cheng Y, Makarov E, Ganesan M, Suemizu H, et al. Human hepatocyte depletion in the presence of HIV-1 infection in dual reconstituted humanized mice. Biol Open. 2018;7(2). https://doi.org/10.1242/bio.029785
26. Ganesan M, Tikhanovich I, Vangimalla SS, Dagur RS, Wang W, Poluektova LI, et al. Demethylase JMJD6 as a New Regulator of Interferon Signaling: Effects of HCV and Ethanol Metabolism. Cell Mol Gastroenterol Hepatol. 2018;5(2):101-12. https://doi.org/10.1016/j.jcmgh.2017.10.004
27. Tyagi RK, Tandel N, Deshpande R, Engelman RW, Patel SD, Tyagi P. Humanized Mice Are Instrumental to the Study of Plasmodium falciparum Infection. Front Immunol. 2018;9:2550. https://doi.org/10.3389/fimmu.2018.02550
28. Yamazaki-Nishioka M, Shimizu M, Suemizu H, Nishiwaki M, Mitsui M, Yamazaki H. Human plasma metabolic profiles of benzydamine, a flavin-containing monooxygenase probe substrate, simulated with pharmacokinetic data from control and humanized-liver mice. Xenobiotica. 2018;48(2):117-23. https://doi.org/10.1080/00498254.2017.1288280
29. Dagur RS, Wang W, Makarov E, Sun Y, Poluektova LY. Establishment of the Dual Humanized TK-NOG Mouse Model for HIV-associated Liver Pathogenesis. J Vis Exp. 2019(151). https://doi.org/10.3791/58645
30. Doi A, Hikita H, Kai Y, Tahata Y, Saito Y, Nakabori T, et al. Combinations of two drugs among NS3/4A inhibitors, NS5B inhibitors and non-selective antiviral agents are effective for hepatitis C virus with NS5A-P32 deletion in humanized-liver mice. J Gastroenterol. 2019;54(5):449-58. https://doi.org/10.1007/s00535-018-01541-x
31. Iwata H, Goto M, Sakai N, Suemizu H, Yamazaki H. Predictability of human pharmacokinetics of diisononyl phthalate (DINP) using chimeric mice with humanized liver. Xenobiotica. 2019;49(11):1311-22. https://doi.org/10.1080/00498254.2018.1564087
32. Uehara S, Yoneda N, Higuchi Y, Yamazaki H, Suemizu H. Human Aldehyde Oxidase 1-Mediated Carbazeran Oxidation in Chimeric TK-NOG Mice Transplanted with Human Hepatocytes. Drug Metab Dispos. 2020;48(7):580-6. https://doi.org/10.1124/dmd.120.091090
33. Uehara S, Yoneda N, Higuchi Y, Yamazaki H, Suemizu H. Metabolism of desloratadine by chimeric TK-NOG mice transplanted with human hepatocytes. Xenobiotica. 2020;50(6):733-40. https://doi.org/10.1080/00498254.2019.1688892
34. Wang W, Smith N, Makarov E, Sun Y, Gebhart CL, Ganesan M, et al. A long-acting 3TC ProTide nanoformulation suppresses HBV replication in humanized mice. Nanomedicine. 2020;28:102185. https://doi.org/10.1016/j.nano.2020.102185
35. Zhang LL, Li JL, Ji MX, Tian D, Wang LY, Chen C, et al. Attenuated P. falciparum Parasite Shows Cytokine Variations in Humanized Mice. Front Immunol. 2020;11:1801. https://doi.org/10.3389/fimmu.2020.01801
36. Kanbe A, Ishikawa T, Hara A, Suemizu H, Nanizawa E, Tamaki Y, et al. Novel hepatitis B virus infection mouse model using herpes simplex virus type 1 thymidine kinase transgenic mice. J Gastroenterol Hepatol. 2021;36(3):782-9. https://doi.org/10.1111/jgh.15142
37. Ma Y, Jiang CF, Li P, Cao H. In Vivo Functional Analysis of Nonconserved Human lncRNAs Using a Humanized Mouse Model. Methods Mol Biol. 2021;2254:339-47. https://doi.org/10.1007/978-1-0716-1158-6_21
38. Miyamoto M, Kosugi Y, Iwasaki S, Chisaki I, Nakagawa S, Amano N, et al. Characterization of plasma protein binding in two mouse models of humanized liver, PXB mouse and humanized TK-NOG mouse. Xenobiotica. 2021;51(1):51-60. https://doi.org/10.1080/00498254.2020.1808735
39. Sari G, van Oord GW, van de Garde MDB, Voermans JJC, Boonstra A, Vanwolleghem T. Sexual Dimorphism in Hepatocyte Xenograft Models. Cell Transplant. 2021;30:9636897211006132. https://doi.org/10.1177/09636897211006132
40. Tyagi RK. Plasmodium falciparum-infected humanized mice: a viable preclinical tool. Immunotherapy. 2021;13(16):1345-53. https://doi.org/10.2217/imt-2021-0102
41. Uehara S, Higuchi Y, Yoneda N, Yamazaki H, Suemizu H. UDP-glucuronosyltransferase 1A4-mediated N2-glucuronidation is the major metabolic pathway of lamotrigine in chimeric NOG-TKm30 mice with humanised-livers. Xenobiotica. 2021;51(10):1146-54. https://doi.org/10.1080/00498254.2021.1972492
42. Uehara S, Yoneda N, Higuchi Y, Yamazaki H, Suemizu H. Methyl-hydroxylation and subsequent oxidation to produce carboxylic acid is the major metabolic pathway of tolbutamide in chimeric TK-NOG mice transplanted with human hepatocytes. Xenobiotica. 2021;51(5):582-9. https://doi.org/10.1080/00498254.2021.1875515
43. Uehara S, Yoneda N, Higuchi Y, Yamazaki H, Suemizu H. Oxidative metabolism and pharmacokinetics of the EGFR inhibitor BIBX1382 in chimeric NOG-TKm30 mice transplanted with human hepatocytes. Drug Metab Pharmacokinet. 2021;41:100419. https://doi.org/10.1016/j.dmpk.2021.100419
44. Bachour-El Azzi P, Chesne C, Uehara S. Expression and functional activity of cytochrome P450 enzymes in human hepatocytes with sustainable reproducibility for in vitro phenotyping studies. Adv Pharmacol. 2022;95:285-305. https://doi.org/10.1016/bs.apha.2022.05.009
45. Cho N, Suemizu H, Kamimura H, Ohe T, Ito F, Akita H, et al. Formation of reactive metabolites of benzbromarone in humanized-liver mice. Drug Metab Pharmacokinet. 2022;47:100467. https://doi.org/10.1016/j.dmpk.2022.100467
46. Das S, Wang W, Ganesan M, Fonseca-Lanza F, Cobb DA, Bybee G, et al. An ultralong-acting tenofovir ProTide nanoformulation achieves monthslong HBV suppression. Sci Adv. 2022;8(51):eade9582. https://doi.org/10.1126/sciadv.ade9582
47. Uehara S, Higuchi Y, Yoneda N, Kawai K, Yamamoto M, Kamimura H, et al. An improved TK-NOG mouse as a novel platform for humanized liver that overcomes limitations in both male and female animals. Drug Metab Pharmacokinet. 2022;42:100410. https://doi.org/10.1016/j.dmpk.2021.100410
48. Uehara S, Iida Y, Ida-Tanaka M, Goto M, Kawai K, Yamamoto M, et al. Humanized liver TK-NOG mice with functional deletion of hepatic murine cytochrome P450s as a model for studying human drug metabolism. Sci Rep. 2022;12(1):14907. https://doi.org/10.1038/s41598-022-19242-0
49. Uehara S, Suemizu H, Yamazaki H. Cytochrome P450s in chimeric mice with humanized liver. Adv Pharmacol. 2022;95:307-28. https://doi.org/10.1016/bs.apha.2022.05.004
50. Uehara S, Yoneda N, Higuchi Y, Yamazaki H, Suemizu H. Cytochrome P450-dependent drug oxidation activities and their expression levels in liver microsomes of chimeric TK-NOG mice with humanized livers. Drug Metab Pharmacokinet. 2022;44:100454. https://doi.org/10.1016/j.dmpk.2022.100454
51. Uehara S, Higuchi Y, Yoneda N, Kato H, Yamazaki H, Suemizu H. The Unique Human N10-Glucuronidated Metabolite Formation from Olanzapine in Chimeric NOG-TKm30 Mice with Humanized Livers. Drug Metab Dispos. 2023;51(4):480-91. https://doi.org/10.1124/dmd.122.001102
52. Yokota Y, Suzuki S, Gi M, Yanagiba Y, Yoneda N, Fujioka M, et al. o-Toluidine metabolism and effects in the urinary bladder of humanized-liver mice. Toxicology. 2023;488:153483. https://doi.org/10.1016/j.tox.2023.153483
53. Zerdoug A, Le Vee M, Uehara S, Jamin A, Higuchi Y, Yoneda N, et al. Drug transporter expression and activity in cryopreserved human hepatocytes isolated from chimeric TK-NOG mice with humanized livers. Toxicol In Vitro. 2023;90:105592. https://doi.org/10.1016/j.tiv.2023.105592
54. Abe-Chayama H, Kawase T, Ichinohe T, Ishida Y, Tateno C, Hijikata M, et al. Hepatitis B virus-specific human stem cell memory T cells differentiate into cytotoxic T cells and eradicate HBV-infected hepatocytes in mice. FEBS Lett. 2024;598(11):1354-65. https://doi.org/10.1002/1873-3468.14842
55. Aslamkhan AG, Michna L, Podtelezhnikov A, Vlasakova K, Suemizu H, Ohnishi Y, et al. A mechanistic biomarker investigation of fialuridine hepatotoxicity using the chimeric TK-NOG Hu-liver mouse model and in vitro micropatterned hepatocyte cocultures. Toxicol Res (Camb). 2024;13(1):tfad120. https://doi.org/10.1093/toxres/tfad120
56. Zerdoug A, Le Vee M, Le Mentec H, Carteret J, Jouan E, Jamin A, et al. Induction of drug metabolizing enzyme and drug transporter expression by antifungal triazole pesticides in human HepaSH hepatocytes. Chemosphere. 2024;366:143474. https://doi.org/10.1016/j.chemosphere.2024.143474
57. Miyake T, Tsutsui H. Quantitative prediction of human pharmacokinetic drug-drug interactions and drug clearance using humanized liver chimeric mice: a review. Drug Metab Pharmacokinet. 2026;67:101517. https://doi.org/10.1016/j.dmpk.2026.101517
58. Shimoda A, Murai K, Hikita H, Minami S, Miyake T, Kuriki S, et al. Auranofin, identified by FDA-approved drug library screening, inhibits HBs antigen secretion via lysosomal damage. PLoS One. 2026;21(1):e0340023. https://doi.org/10.1371/journal.pone.0340023
