C57BL/10 Targeted Mutation Mouse Strain that Develops Spontaneous Keratitis

Tech ID: 08-12

Summary
Research scientists at National Jewish Health have developed a C57BL/10 targeted mutation mouse strain that expresses defective T cell receptors and spontaneously develop keratitis. Genes from mice of the C57BL/6 background, which carry existing genetically engineered mutations that prevent the development of?d or aß T cells, were transferred onto the C57BL/10 background.

Potential Applications

Animal model for keratitis where the development is spontaneous
A model to test compounds developed to treat keratitis or influence angiogenesis

Advantages of Invention
B10.TCR d -/- and B10-TCR ß-/- female mice show a high frequency of spontaneous keratitis. The B10.TCR ß/d -/- females have a lower incidence of spontaneous keratitis.

State of Development
To establish new C57BL/10 background mouse strains, ten or more backcrosses were carried out. The B10.TCR d -/- mice have defective T cell receptor-Cd gene; the B10-TCR ß-/- mice have defective T cell receptor Cß gene. These mice were intercrossed to establish the B10.TCR ß/d -/- strain.

B10.TCR d-/- and B10.TCR b-/- mice develop a spontaneous eye disease at a high frequency. Left - normal C57BL/10 eye. Right - B10.TCR d-/- mice showing corneal opacity. Note the central thickening.

Histological sections (H&E stained) showing that the corneal opacity in these mice is due to keratitis. 1 and 2, normal C57BL/10 eye shown for comparison. Panels 2-6 are close-ups of the corneal area only, and examples of increasing severity are shown. Note the inflammatory infiltrates in the corneal stroma, also the presence of blood vessels in the stroma, and the occasional thickening of the corneal epithelium.

Publication

O'brien, R. L., M. A. Taylor, J. Hartley, T. Nuhsbaum, S. Dugan, K. Lahmers, M. K. Aydintug, J. M. Wands, C. L. Roark, and W. K. Born. "Protective Role of T Cells in Spontaneous Ocular Inflammation." Investigative Ophthalmology & Visual Science 50.7 (2009): 3266-274. PMID: 19151391

Inventors
Rebecca O'Brien, PhD and Willi Born, PhD

For Further Information, Contact:

Emmanuel Hilaire, PhD
Director
Technology Transfer Office
National Jewish Health
1400 Jackson Street, Room M206b
Denver, CO 80206
Voice: (303) 398-1262
Fax: (303) 270-2352
HilaireE@njhealth.org