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Related Experiment Videos

Mice lacking all conventional MHC class II genes.

L Madsen1, N Labrecque, J Engberg

  • 1Department of Clinical Immunology, Rigshospitalet, 2200 Copenhagen, Denmark.

Proceedings of the National Academy of Sciences of the United States of America
|September 1, 1999
PubMed
Summary

Researchers created knockout mice lacking all major histocompatibility complex class II (MHC-II) genes. These mice, devoid of MHC-II, are valuable for studying human autoimmune diseases and immune responses.

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Area of Science:

  • Immunology
  • Genetics

Background:

  • Major histocompatibility complex class II (MHC-II) molecules are crucial for T cell repertoire selection, adaptive immunity, and autoimmune regulation.
  • Existing knockout models have limitations in studying MHC-II functions and human disease associations.

Purpose of the Study:

  • To generate a comprehensive mouse model lacking all classical murine MHC-II genes.
  • To assess the utility of these mice for studying human MHC-II-associated autoimmune disorders.

Main Methods:

  • Engineered a large (80-kilobase) deletion of the entire murine MHC-II region using homologous recombination and Cre recombinase-mediated excision.
  • Generated MHCII(Delta/Delta) knockout mice.

Main Results:

  • MHCII(Delta/Delta) mice exhibited immune system perturbations, including a significant reduction in CD4(+) lymphocytes in the thymus and spleen, similar to other MHC-II knockout models.

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  • No new anatomical or physiological abnormalities were observed in these mice.
  • The absence of all classical MHC-II chains, including unpaired ones, makes these mice ideal recipients for MHC-II transgenes from other species.

    • Conclusions:

    • MHCII(Delta/Delta) mice provide a unique model for studying MHC-II function due to the complete absence of endogenous MHC-II chains.
    • These mice are invaluable for creating "humanized" mouse models to investigate human MHC-II-associated autoimmune disorders and immune responses.