Date of Award:
Doctor of Philosophy (PhD)
Reed P. Warren
Reed P. Warren
Robert W. Sidwell
The D-variant of encephalomyocarditis (EMC-D) virus was given to SJUJ mice by the artificial, intraperitoneal (ip) route of infection, or by the natural routes of infection per os (po) or intranasal (i.n .), in comparable concentrations. The po route of infection was found to be ineffective. Mice given virus by either the ip or i.n. routes of infection became diabetic. Mice were more resistant to the infectious and diabetogenic properties of the virus when given by the i.n. than when given by the ip route. Glycosuria in mice given virus i.n. usually lagged one day behind that in mice given virus ip.
Measurement of glucose in mouse urine by use of Diastix® reagent strips was found to be a reliable indicator of diabetes. This test was easily and quickly accomplished without harm or pain to the mice.
Crude virus preparations were compared to purified virus preparations for their diabetogenic and infectious properties in mice. No statistically significant differences in either parameter were observed. Virus prepared by a single passage in BHK-21 cells was fully diabetogenic, contrary to a previously published report.
Male SJUJ mice were infected with a diabetogenic dose of EMC-D virus by the i.n. route. Relative times of development of virus infection and mouse resistance parameters were compared to the time of development of signs of diabetes in the mice. A rapid decrease of plasma interferon titer corresponded to the time of development of signs of diabetes in the infected mice. Whether this was coincidental or has some significance in development of diabetes is unknown.
Tissue sections from pancreas, spleen , kidney, liver, lung , heart, and thymus were studied by immunohistochemical staining techniques for the presence of virus antigen, insulin, and the three types of mouse interferon (α, β, and γ).
Glucose was excreted in the saliva of mice with glycosuria. Previous reports of this excretion in diabetic mice have not been found in the literature. Mice without glycosuria did not excrete measurable (by Clinistix® or Diastix®) glucose in saliva.
Some mice were able to control the polyuria, polydipsia, and polyphagia normally seen in diabetes mellitus. These mice eventually reverted from having signs of diabetes to a normal state of plasma glucose and urine devoid of glucose. The mechanisms by which the mice were able to do this are unknown at this time.
Huffman, John Henry, "Studies on Encephalomyocarditis Virus-Induced Diabetes in Mice" (1988). All Graduate Theses and Dissertations. 4046.
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