Establishment of the dual humanized TK-NOG mouse model for HIV-associated liver pathogenesis

Raghubendra Singh Dagur, Weimin Wang, Edward Makarov, Yimin Sun, Larisa Y. Poluektova

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Despite the increased life expectancy of patients infected with human immunodeficiency virus-1 (HIV-1), liver disease has emerged as a common cause of their morbidity. The liver immunopathology caused by HIV-1 remains elusive. Small xenograft animal models with human hepatocytes and human immune system can recapitulate the human biology of the disease's pathogenesis. Herein, a protocol is described to establish a dual humanized mouse model through human hepatocytes and CD34+ hematopoietic stem/progenitor cells (HSPCs) transplantation, to study liver immunopathology as observed in HIV-infected patients. To achieve dual reconstitution, male TK-NOG (NOD.Cg-Prkdcscid Il2rgtm1Sug Tg(Alb-TK)7-2/ShiJic) mice are intraperitoneally injected with ganciclovir (GCV) doses to eliminate mouse transgenic liver cells, and with treosulfan for nonmyeloablative conditioning, both of which facilitate human hepatocyte (HEP) engraftment and human immune system (HIS) development. Human albumin (ALB) levels are evaluated for liver engraftment, and the presence of human immune cells in blood detected by flow cytometry confirms the establishment of human immune system. The model developed using the protocol described here resembles multiple components of liver damage from HIV-1 infection. Its establishment could prove to be essential for studies of hepatitis virus co-infection and for the evaluation of antiviral and antiretroviral drugs.

Original languageEnglish (US)
Article numbere58645
JournalJournal of Visualized Experiments
Issue number151
StatePublished - 2019


  • Albumin
  • Dual humanized mice
  • Hematopoietic progenitor cells
  • Hematopoietic stem cells
  • Hepatocytes
  • Human immune system
  • Human immunodeficiency virus-1 (HIV-1)
  • Humanized liver
  • Immunology and Infection
  • Issue 151

ASJC Scopus subject areas

  • General Neuroscience
  • General Chemical Engineering
  • General Biochemistry, Genetics and Molecular Biology
  • General Immunology and Microbiology


Dive into the research topics of 'Establishment of the dual humanized TK-NOG mouse model for HIV-associated liver pathogenesis'. Together they form a unique fingerprint.

Cite this