Genes for immunoglobulin heavy chain and serum prealbumin protein are linked in mouse.
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Biomedical subjects
Publications and source records attributed to M Cherry.
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A new locus is described that determines an alloantigen on the surface of lymphocytes. It differs from loci previously described in that the corresponding antibody, at least in most antisera, reacts almost exclusively with node lymphocytes, and weakly or not at all with thymuslymphocytes. Positive strains include C57BL/6, C57BL/10, C57L, C57BR/cd, and RF; negative strains include BALB/c, C3H, and SJL. The symbol Ly-4 is assigned, with the C57BL/6 allele being Ly-4(b), and the BALB/c allele Ly-4(a).
We analyzed the relationship of genetic factors determining the expression of endogenous type-C RNA tumor viruses and other host-gene markers to tumorigenesis. A hybridization experiment was performed with mice of strains AKR/J and C57L, the first filial (F(1)) generation hybrids, the second filial (F(2)) generation hybrids, and the backcrosses to the two parental strains. The results demonstrated a highly significant and predictable association between the expression of complete infectious virus or the viral group-specific (gs) antigen in spleens of young mice and tumorigenesis later in life. Most of the tumors were thymic leukemia and reticulum sarcoma, but other mesenchymal, as well as epithelial, tumors were also observed. Tumors occurred preferentially in gs-antigen- or virus-positive mice of all crosses; in the C57L-backcross and F(2) mice segregating for gs-antigen and virus expression, a few gs-antigen-negative mice developed reticulum cell sarcomas. At the time of their occurrence, the mice were all gs-antigen-positive, and most had virus as well.A minor effect of the major histocompatibility locus, H-2, on leukemogenesis was found in the F(2) mice. Several tumor types were also found that we have never observed in the two parental strains. Our data provide the most direct biological evidence in favor of the viral oncogene theory. Thus, from the presence or absence of expression in early life of splenic gs antigen or virus, we can predict whether or not a tumor is likely to develop later in life. These findings suggest that the genome of endogenous type-C RNA viruses is the major determinant for tumorigenesis although they provide no clues about the factors responsible for the various histological types.
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H-2 alloantigens in an intact, undegraded form can be solubilized by the nonionic detergent NP-40 and isolated by indirect immunoprecipitation and electrophoresis in sodium dodecyl sulfate on polyacrylamide gels. With the use of an immunological precipitation method, the question about the number of cellular H-2 gene products in heterozygous cells has been partially resolved. At least four separable gene products were detected in cells heterozygous at the H-2 genetic region-one for each of the H-2D genes of the two parental haplotypes, and one for each of the H-2K genes of the two parental haplotypes. This is in contrast to the two H-2 gene products reported previously for cells homozygous at the H-2 region. The findings establish that the two parental H-2 haplotypes on homologous chromosomes in heterozygous cells are ultimately expressed as different glycoprotein molecules.
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Serum samples from about 10 males and 10 females from each of 16 genetically defined strains of rabbits and from one hybrid were tested as sources of complement for the microtiter lymphocytotoxicity test. Lymph nodes from mice of strain B10.A/Sn were used as the target cells with a strong H-2 alloantiserum. Results indicate marked strain differences. Rabbit serum from a hybrid between the two best strains IIIC/J and IIIVO/J was almost as satisfactory as the parental strains and better than all other strains tested in this system, indicating a genetic basis for the response. The results of testing aliquots of these serum samples against other test systems including human cell lines will have to be in hand before a general statement can be made, but preliminary unpublished data against lymph nodes from A/HeJ and C3H/HeJ strain mice and tumor cells from an ascites form of a sarcoma Sal-A are encouraging and suggest a consistent superiority of the two strains and the hybrid between them referred to above.
Serum samples from about 10 males and 10 females from each of 15 genetically defined strains of rabbits and from one hybrid were tested as sources of complement for the microtiter lymphocytotoxicity test using as target cells lymph node cells from C3H/HeJ, B10/Sn, BALB/cJ, and DBA/2J strain mice. The lynph node cells were tested with appropriate H-2 alloantisera. Results indicated marked strain differences. Correlation analysis of these data with data using primarily aliquots from the same serum samples tested against lymph node cells from B10.A/Sn mice showed clearly that a genetically defined population of rabbits that provided serum of high quality for one of these test systems would in general work reasonably well in any one of the other four. The correlation coefficients in all possible combinations ranged from +0.49 to +0.92. Of the five strains tested, the results obtained from BALB/cJ appear to be the best predictors of the results in the other four strains (r values were +0.74, +0.57, "0.76, and +0.92). Studies are in progress to test rabbit serum complement samples against the more demanding tumor cells.