International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


POSTER 32 - RESISTANCE AGAINST TNF-INDUCED LETHAL INFLAMMATION: DISCREPANCY BETWEEN RECOMBINANT INBRED DATA AND BACKCROSS/INTERCROSS DATA.

Dr. Claude Libert
Mouse Molecular Genetics Unit
VIB-Department Molecular Biology
Ledeganckstraat, 35
9000 Ghent
Belgium

Co-Authors: Ben Weilochx
Institution: Mouse Molecular Genetics Unit, VIB

We found that DBA/2J mice (D2/J) exhibit a four-fold reduced sensitivity to tumor necrosis factor (TNF)-induced lethal inflammatory shock, compared to C57BL/6J (B6/J). The dominant trait was also reflected in the hypothermia and induction of IL-6. The entire set of BXD recombinant inbred (RI) mice was tested and the resulting strain-distribution-pattern (SDP) was closely linked with a locus on distal chromosome 12, TNFp, for TNF-protection. However a close look at the lethality data showed that several strains behaved as parental strains (16 strains) and that some had an intermediate phenotype. Using Mapmanager another protective locus on chromosome 6 appears (Cmv1), but only when the 16 best BXD strains are considered. Several BDJB backcrosses were performed, and also, in a collaborative effort with Dr. R. Williams (University of Tennessee, TN, USA), experiments were performed using advanced intercross mice (at the F9 generation). However, the data were difficult to analyze, because the window between the parental strains is too narrow. DBA/2Crl mice from Charles River were found to resist significantly better to TNF, compared to DBA/2J. The difference between D2/J and D2/Crl is fascinating and probably due to genetic drift : D2/J and D2/Crl lines have separated in 1948.


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