The overall purpose of the Animal Model Core is to perform all of the animal experimentation which is a significant part of Projects 1-3 and to provide appropriate specimens to the investigators in those projects for further analysis. While the mouse model for chlamydial genital Infection is commonly used by a number of laboratories, there are only few with any experience using the guinea pig model and none to our knowledge currently using the model. The P.I. of this core developed the guinea pig model of chlamydial genital infection together with the late Dr. Almen Barron and over a 32 year period has extensively characterized the model with respect to the host immune response, the pathogenesis of ascending infection, the effect of reproductive hormones and the pathologic response in the female. Moreover, the P.I. has developed and characterized the host response and pathogenesis of infection in the male urethra as well as published studies using the conjunctival model of chlamydial infection. Finally, this laboratory has developed the methodology and demonstrated that sexual transmission of chlamydial infection from male to female guinea pigs can be reliably accomplished. Thus, this laboratory has unique experience with the guinea pig model which will allow it to support the primary projects in this proposal. Another resource available to this core which will be utilized in each of the projects is a frozen stock of C. caviae from November 13, 1989. This stock is a yolk sac suspension which is a direct lineage from the original Murray isolate. The unique aspect of this stock is in fact that it and its predecessors were cultured exclusively in chick embryos, obviously a living animal, so it has never been in tissue culture. Thus, any selective pressures specific for tissue culture will not have had an influence on the chlamydial variants in this stock. This stock will be expanded and used as the initial inoculum in Project 2 and will be used as a standard for all comparisons with mutants produced in Project 3. Each of the projects within this proposal has specific requirements so the specific aim of the Animal Model Core will be to provide the specimens and in vivo data necessary to support those projects and, in particular, parallel as best as possible, the specimens and data obtained from human subjects.
The guinea pig model of chlamydial genital infection is an ideal model in which to study the pathogenesis of chlamydial infection. Because the reproductive physiology and the normal fiora of the guinea female genital tract is similar to human, it allows the study of the microbiota and the effect of chlamydial infection and hormonal changes. Furthermore, the infection in the male and the effect of sexual transmission can be studied.
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