Spontaneous bacterial keratitis in CD36 knockout mice.
Summary of "Spontaneous bacterial keratitis in CD36 knockout mice."
Purpose: CD36 is a Class B scavenger receptor that is constitutively expressed in the corneal epithelium and has been implicated in many homeostatic functions, including the homeostasis of the epidermal barrier. The aim of this study is to determine (i) whether CD36 is required for the maintenance of the corneal epithelial barrier to infection, and (ii) whether CD36 deficient mice present with an increased susceptibility to bacterial keratitis. Methods: The corneas of CD36-/-, TSP-1-/-, TLR2-/-, and C57BL/6 WT mice were screened via slit lamp microscopy or ex vivo analysis. The epithelial tight junctions and mucin layer were assessed via LC-biotin and Rose Bengal staining, respectively. Bacterial quantification was performed on corneal buttons and S. aureus conjugated to FITC was used to study bacterial binding. Results: CD36-/- mice develop spontaneous corneal defects that increased in frequency and severity with age. The mild corneal defects were characterized by (i) a disruption in epithelial tight junctions and the mucin layer, (ii) an infiltrate of macrophages and (iii) increased bacterial binding. Bacterial quantification revealed high levels of S. xylosus in the corneas of CD36-/- mice with severe defects, but not in WT controls. Conclusion: CD36-/- mice develop spontaneous bacterial keratitis independent of TLR2 and TSP-1. We conclude that CD36 is a critical component of the corneal epithelial barrier and in the absence of CD36 the barrier breaks down allowing bacteria to bind to the corneal epithelium, resulting in spontaneous keratitis. This is the first report of spontaneous bacterial keratitis in mice.
Department of Ophthalmology, Harvard Medical School, Schepens Eye Research Institute, Boston, United States.
This article was published in the following journal.
Name: Investigative ophthalmology & visual science
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20847111
- DOI: http://dx.doi.org/10.1167/iovs.10-5566
Medical and Biotech [MESH] Definitions
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Mice, 129 Strain
Strains of mice arising from a parental inbred stock that was subsequently used to produce substrains of knockout and other mutant mice with targeted mutations.
Mice, Inbred Mdx
A strain of mice arising from a spontaneous MUTATION (mdx) in inbred C57BL mice. This mutation is X chromosome-linked and produces viable homozygous animals that lack the muscle protein DYSTROPHIN, have high serum levels of muscle ENZYMES, and possess histological lesions similar to human MUSCULAR DYSTROPHY. The histological features, linkage, and map position of mdx make these mice a worthy animal model of DUCHENNE MUSCULAR DYSTROPHY.
Leukocyte differentiation antigens and major platelet membrane glycoproteins present on MONOCYTES; ENDOTHELIAL CELLS; PLATELETS; and mammary EPITHELIAL CELLS. They play major roles in CELL ADHESION; SIGNAL TRANSDUCTION; and regulation of angiogenesis. CD36 is a receptor for THROMBOSPONDINS and can act as a scavenger receptor that recognizes and transports oxidized LIPOPROTEINS and FATTY ACIDS.
A broadly expressed type D cyclin. Experiments using KNOCKOUT MICE suggest a role for cyclin D3 in LYMPHOCYTE development.
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