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Sprague Dawley

Fallon K Noto1, Valeriya Adjan-Steffey2, Min Tong3

  • 1Hera BioLabs Inc., Lexington, Kentucky.

Molecular Cancer Therapeutics
|September 13, 2018
PubMed
Summary
This summary is machine-generated.

Researchers developed a novel immunodeficient rat model by deleting the Recombination Activating Gene 2 (Rag2). This new Sprague-Dawley Rag2 knockout rat supports human xenograft growth, advancing preclinical cancer research.

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Area of Science:

  • Immunology
  • Genetics
  • Oncology

Background:

  • Rats are preferred preclinical models for toxicology due to advantages over mice.
  • An immunodeficient rat model is needed for enhanced tumor development and drug efficacy studies.
  • Existing models lack the necessary immunodeficiency for comprehensive xenograft research.

Purpose of the Study:

  • To create a novel immunodeficient rat model for xenograft studies.
  • To validate the utility of this model for human cancer cell line growth.
  • To establish a versatile platform for preclinical cancer research.

Main Methods:

  • Genetically modified rat spermatogonial stem cells (SSCs) using TALENs to delete the Recombination Activating Gene 2 (Rag2).
  • Transplanted modified SSCs into sterile rats and bred offspring to produce homozygous Rag2 knockout rats (SDR).
  • Assessed immunodeficiency by confirming the absence of mature B and T cells and tested xenograft compatibility with human cancer cell lines.

Main Results:

  • Successfully generated the Sprague-Dawley Rag2 knockout (SDR) rat with a functional Rag2 deletion.
  • The SDR rat lacks mature B and T cells, confirming its immunodeficient status.
  • Demonstrated successful subcutaneous tumor formation and growth of human glioblastoma, non-small cell lung cancer, ovarian cancer, and endometrial cancer cell lines.

Conclusions:

  • The Sprague-Dawley Rag2 knockout rat is a viable and effective model for human xenograft studies.
  • This novel immunodeficient rat model supports the growth of diverse human cancer types.
  • The SDR rat facilitates advanced preclinical research, including efficacy and toxicologic studies.