Molecular Biology: Open Access

The immune system is a network of thousands of molecules, cells and regulatory factors that produce many interrelated responses. In this study, we used spot synthesis to map tobacco mosaic virus (TMV) epitopes in a mice animal model (Balb/c) and compared the results with those obtained using immunoinformatic prediction tools. Mice were inoculated with TMV and after immunization the sera were incubated with an array of overlapping pentadecapeptides that corresponded to the full sequence of the TMV capside protein (TMVcp) that had been synthesized on a cellulose membrane for spot synthesis analysis. Six linear epitopes were identified experimentally, as shown by the IgG-elicited immune responses in mice. The data for epitope prediction based on epitope databases agreed with the results obtained by spot synthesis results. Comparison of the findings for spot intensities and those obtained with the prediction software allowed the identification of different responses according to the MHC class I alleles. The results of this work provide a detailed antigenic profile for TMV.

GNE myopathy, or Hereditary Inclusion Body Myopathy (HIBM), is an autosomal recessive adult-onset muscle wasting disorder caused by hypomorphic GNE (UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase), the rate-limiting enzyme of sialic acid (Sia) biosynthesis. Unlike human patients, mice bearing the Gne^M712T/M712T genotype in C57BL/6 background strain suffer severe glomerular hematuria, show incomplete podocyte development, and do not survive beyond the first few days of life. We crossed heterozygous mice (Gne^M712T/+) of B6 strain with FVB strain mice. In mixed inbred FVB; B6 background, the homozygous mice showed attenuated glomerular disease and survived longer (mean survival 23.48 ± 13.99 weeks, n=73). Within the first 2 generations, 26% of the homozygous mice survived past the age of 40 weeks, and within the subsequent 3 generations the frequency of homozygous mice surviving past age of 40 weeks had increased to 44%. Additionally, the homozygous mice (Gne^M712tM712t) living past the age of 42 weeks began to show muscle pathology. These findings suggest that the mouse background strain affects the disease phenotype, and that natural selection may have an influence on the long-term maintenance of mouse models of human disease.