International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)

Table of Contents * Complex Genetics * Developmental Genetics * Gene Annotation * Gene Discovery * Genome Sequencing * Functional Genomics * Mutagenesis * Presentations * Verne Chapman Memorial Lecture

Mr Eduardo Diez
McGill University
3655 Sir William Osler
Room 910
Montreal
H3G 1Y6
Canada

Co-Authors:  2)Yaraghi Z, 2&3)MacKenzie A, 1)Gros P, 1)Vidal S, 1)Lee SH
Institutions: 1)Department of Biochemistry, McGill University, 2)Department of Biochemistry & Pediatrics, University of Ottawa, 3)Apoptogen Inc

Towards the identification of the natural host resistance gene lGN1  (Work in progress)

Legionella pneumophila is an intracellular pathogen that causes Legionnaires' disease in humans. Segregation analyses using macrophages from susceptible and resistant inbred mice have indicated that a single recessive gene, designated Lgn1, determines permissiveness to intracellular replication of L. pneumophila.

The Lgn1 critical genetic interval has been narrowed to 0.32 cM within distal mouse Chromosome 13. This genomic region corresponds to an Lgn1 physical interval of about 140 Kb in size and contains the Neuronal Apoptosis Inhibitor Protein (Naip) genes Naip2 and Naip5.

RNA and protein expression studies show Naip presence in mouse macrophages. But the lack of any obvious mutations in the coding sequences of either of the two genes, does not discriminate between the two candidates for a formal identification of the Lgn1 gene.

Transfer of BAC clones from the critical interval into transgenic mice is currently being used to determine whether the Lgn1 susceptibility phenotype of A/J mice can be corrected by BAC clones from non-permissive origins. We are hoping that this approach will soon help us to determine which of the two Naip genes (if not both) actually controls intracellular L. pneumophila replication. In the meantime, Naip2 and Naip5 cDNA cloning and transfection into permissive cell-lines are also being carried out to resolve this issue.