It was originally observed, during kinetic studies of infection, that the intravenous injection of a small inoculum of dispersd Mycobacterium bovis (BCG) cells resulted in one of two distinct patterns of multiplication (growth vs non-growth) in the liver and spleen of mice of several inbred strains. Twenty-four inbred strains of mice which were so examined exhibited marked discontinuous variation in their level of early resistance to BCG infection, as estimated by the number of viable bacilli recovered from the spleen three weks after the intravenous injection of 2.5 x 10('4) BCG. The nature of this genetic variation was then investigated by a Mendelian segregation analysis: resistance of F(,1), F(,2) and backcross progeny bred from representative resistant and susceptible progenitors showed that the trait of resistance was controlled by a single, dominant, autosomal gene, designated Bcg. This gene exists in two allelic forms, Bcg('s) (susceptibility) and Bcg('r) (resistance). The Bcg locus was subsequently mapped to the Chromosome 1 after comparison of the respective strain distribution pattern (SDP) of the previously-mapped Idh-1 and Pep-3 alleles with that of Bcg alleles among mice of BXH and BXD recombinant inbred strains. Strong linkage between the Bcg gene and 2 other host resistance genes, namely Ity and Lsh, was detected by comparison of their respective SDP's. This tight linkage or identity was further confirmed by formal Bcg-Ity-Lsh linkage analysis performed on individual animals of the segregating populations and on inbred mouse strains congenic but for this portion of the first chromosome. / The phenotypic expression of the Bcg locus at the cellular level was investigated in vivo: the cell responsible for early resistance was found not to be a T-cell and most probably not a B cell. The genetically-controlled mechanism of defense proved to be resistant to 950 rads of X-irradiation and susceptible to the toxic effect of silica. The reticuloendothelial system of both Bcg('r) and Bcg('s) strains showed an equal ability to clear a bacterial inoculum from their blood and these animals were also comparable in the intensity of the inflammatory response to an intraperitoneal inoculum of BCG. Explanted pleural and peritoneal resident macrophages supported equally well, independently of their genotype, the intracellular growth of various strains of mycobacteria in vitro.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.71810 |
| Date | January 1982 |
| Creators | Gros, Philippe. |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 000168870, proquestno: AAINK64379, Theses scanned by UMI/ProQuest. |
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