Columbia Technology Ventures

Mouse model for studying immune system lineages

This technology is a mouse model specifically for T-box 21 gene, which encodes a transcription factor for gene expression in many cell types of the immune system.

Unmet Need: Breedable mouse model for key regulatory T cell transcription factor

Current methods to study immune system lineages need accurate mouse models to progress from in vitro data to in vivo experiments and analysis. T-box 21, or Tbx21, encodes a recently identified T cell transcription factor that regulates the T helper 1 cell lineage commitment, and plays an important role in bridging cells of the adaptive and innate immune system. Given the complex transcriptional networks and shared innate and adaptive immune mechanisms that are regulated by T-bet, Tbx21 deficiencies can result in differences in infection responses. Namely, T-bet deficient mice exhibit greater resistance to several inflammatory and autoimmune diseases, such as inflammatory bowel diseases, systemic lupus erythematosus, and type 1 diabetes, and the understanding of the underlying immune mechanism could provide better insight into these disease states.

The Technology: Breedable mouse model with capacity for tissue-specific knockout Tbx21

This mouse model has loxP sites flanking exons 2-6 of Tbx21, which encodes a transcription factor controlling gene expression in many immune cell types. Mice homozygous for this allele are viable and fertile and can be bred with mice expressing specific recombinase such that resulting offspring will have Tbx21 deletions. Thus, the resulting T cell-specific Tbx21 deficient mice will exhibit alteration in their response to some infections, and can serve as useful research models for understanding immune cell differentiation or for modeling clinical immune responses of interest.

This technology has been validated in vivo, with an established colony of the mouse model homozygous for the floxed allele. The mouse model has also been genotyped and deposited at the Jackson Laboratory.

Applications:

  • Research model for immune cell differentiation
  • Research tool for T cell immune response and immune dysfunction
  • Research model of relevant clinical syndromes, such as the role of T-bet in greater resistance to IBD, experimental autoimmune encephalomyelitis (EAE), arthritis, systemic lupus erythematosus, and type 1 diabetes

Advantages:

  • Well validated animal model
  • Well controlled and authenticated husbandry and genotyping
  • Allows selective deletion only in tissues of interest when bred to mice expressing Cre recombinase

Lead Inventor:

Steven Reiner, M.D.

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