Related Experiment Video

Updated: Jun 14, 2025

Chronic, Acute, and Reactivated HIV Infection in Humanized Immunodeficient Mouse Models
09:54

Chronic, Acute, and Reactivated HIV Infection in Humanized Immunodeficient Mouse Models

Published on: December 3, 2019

9.0K

Apobec-mediated retroviral hypermutation in vivo is dependent on mouse strain

Hyewon Byun1, Gurvani B Singh1, Wendy Kaichun Xu1

  • 1Department of Molecular Biosciences, The University of Texas at Austin, Austin, Texas, United States of America.

Plos Pathogens
|August 29, 2024
PubMed

Insights

Mouse mammary tumor virus (MMTV) Rem protein impacts tumorigenesis independently of Apobec3-mediated viral mutagenesis. In C57BL/6 mice, Rem loss accelerated tumor development, but proviral mutations were unaffected, unlike in BALB/c mice.

Area of Science:

  • Virology
  • Immunology
  • Oncology

Background:

  • Murine Apobec3 (mA3) antagonizes mouse mammary tumor virus (MMTV) replication.
  • MMTV-encoded Rem protein inhibits Apobec-mediated proviral mutagenesis in BALB/c mice.
  • The role of Rem in MMTV tumorigenesis in different mouse strains requires further investigation.

Purpose of the Study:

  • To investigate the in vivo role of MMTV Rem protein in tumorigenesis using C57BL/6 (B6) mice.
  • To compare MMTV susceptibility and tumor development in B6 mice versus BALB/c mice.
  • To determine if Rem-mediated effects on tumorigenesis are linked to Apobec-mediated proviral hypermutation in B6 mice.

Main Methods:

  • Infection of wild-type B6, AID-knockout B6, and B6 μMT mice with MMTV strains TBLV-WT (wild-type Rem) and TBLV-SD (Rem-defective).
  • Analysis of tumor development, proviral mutations (high-throughput sequencing), and Apobec3 (mA3) and activation-induced cytidine deaminase (AID) expression (ex vivo stimulation).
  • RNA-sequencing (RNA-Seq) of tumor tissues to identify differentially expressed genes and signaling pathways.

Main Results:

  • B6 mice showed increased susceptibility to MMTV infection and tumorigenesis compared to BALB/c mice.
  • Rem deficiency in TBLV-SD accelerated tumorigenesis in B6 mice, irrespective of AID status.
  • Proviral G-to-A/C-to-T mutations were not dependent on Rem in B6 tumors, but AID and mA3 knockout reduced mutations.
  • B6 splenocytes exhibited higher mA3 relative to AID levels compared to BALB/c.
  • RNA-Seq revealed increased growth factor and cytokine signaling transcripts in TBLV-SD tumors.

Conclusions:

  • Rem-mediated effects on MMTV tumorigenesis in B6 mice are independent of Apobec-mediated proviral hypermutation.
  • The distinct responses in B6 versus BALB/c mice highlight strain-specific differences in MMTV pathogenesis.
  • Rem may influence MMTV tumorigenesis through mechanisms other than direct inhibition of Apobec-mediated mutagenesis, potentially involving growth factor and cytokine signaling.

More Related Videos

Humanized NOD/SCID/IL2rγnull (hu-NSG) Mouse Model for HIV Replication and Latency Studies07:10

Humanized NOD/SCID/IL2rγnull (hu-NSG) Mouse Model for HIV Replication and Latency Studies

Published on: January 7, 2019

15.6K
Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes08:12

Assessing Somatic Hypermutation in Ramos B Cells after Overexpression or Knockdown of Specific Genes

Published on: November 1, 2011

19.9K

Related Concept Videos

Mouse Models of Cancer Study02:43

Mouse Models of Cancer Study

Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
5.5K
In-vitro Mutagenesis01:16

In-vitro Mutagenesis

To learn more about the function of a gene, researchers can observe what happens when the gene is inactivated or “knocked out,” by creating genetically engineered knockout animals. Knockout mice have been particularly useful as models for human diseases such as cancer, Parkinson’s disease, and diabetes.
13.9K
Mismatch Repair01:20

Mismatch Repair

Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
4.8K