BACKGROUND: p8 is a DNA-binding protein induced in many tissues in response to @entity558 treatment. Hence, p8 could be a mediator of @entity558 -associated effects or, on the contrary, p8 expression may be part of the protective mechanism of the tissues in response to @entity558 . Finally, p8 expression in response to @entity558 could also be a simple epiphenomenon. METHODS: To investigate the role of p8 in vivo, we generated p8-deficient @entity19 by gene targeting. Because p8 is a stress protein, we analyzed the response of p8-/- @entity19 to a systemic stress induced by @entity558 injection. Liver was chosen as model organ to monitor alterations in gene expression. RESULTS: @entity558 resulted in higher serum @entity637 concentration and higher mortality rate in p8-deficient @entity19 than in wild-type. Also, liver and pancreas, but not lung, from p8-/- @entity19 showed increased amounts of @entity10873 and HPO. To gain insight into the molecular bases of such susceptibility, we used high density DNA microarrays consisting of ~6000 genes and ESTs to compare gene regulation in response to @entity558 in p8+/+ and p8-/- livers. In wild-type, 105 genes and 73 ESTs were up-regulated and 232 genes and 138 ESTs down-regulated. By contrast, 212 genes and 125 ESTs were found up-regulated and 90 genes and 85 ESTs down regulated in p8-/- @entity19 . Among them, only 93 (51 induced and 42 repressed) corresponded to the wild-type pattern, demonstrating that p8 deficiency hinders the normal response to @entity558 , which may account for the increased sensitivity of p8-/- @entity19 to the endotoxin. CONCLUSIONS: The large number of genes showing abnormal regulation after @entity558 suggests that p8 is an important regulatory factor involved in many cellular defence pathways.

XXXX with targeted disruption of p8 gene show increased sensitivity to lipopolysaccharide and DNA microarray analysis of livers reveals an aberrant gene expression response.

@entity19 :: ('10090', 'Species') :: ['mice'] @entity558 :: ('MESH:C536528', 'Disease') :: ['LPS'] @entity10873 :: ('17523(Tax:10090)', 'Gene') :: ['MPO'] @entity637 :: ('21926(Tax:10090)', 'Gene') :: ['TNF-alpha']
@entity19 :: (10090,Species) :: ['Mice']
