title: Phenotyping of Nod1/2 double deficient mice and characterization of Nod1/2 in systemic inflammation and associated renal disease.
abstract: It is indispensable to thoroughly characterize each animal model in order to distinguish between primary and secondary effects of genetic changes. The present study analyzed Nod1 and Nod2 double deficient (Nod1/2 DKO) mice under physiological and inflammatory conditions. Nod1 and Nod2 are members of the Nucleotide-binding domain and Leucine-rich repeat containing Receptor (NLR) family. Several inflammatory disorders, such as Crohn's disease and asthma, are linked to genetic changes in either Nod1 or Nod2. These associations suggest that Nod1 and Nod2 play important roles in regulating the immune system.Three-month-old wildtype (Wt) and Nod1/2 DKO mice were sacrificed, body and organ weight were determined, and blood was drawn. Except for lower liver weight in Nod1/2 DKO mice, no differences were found in body/organ weight between both strains. Leukocyte count and composition was comparable. No significant changes in analyzed plasma biochemical markers were found. Additionally, intestinal and vascular permeability was determined. Nod1/2 DKO mice show increased susceptibility for intestinal permeability while vascular permeability was not affected. Next we induced septic shock and organ damage by administering LPS+PGN intraperitoneally to Wt and Nod1/2 DKO mice and sacrificed animals after 2 and 24 hours. The systemic inflammatory and metabolic response was comparable between both strains. However, renal response was different as indicated by partly preserved kidney function and tubular epithelial cell damage in Nod1/2 DKO at 24 hours. Remarkably, renal inflammatory mediators Tnfα, KC and Il-10 were significantly increased in Nod1/2 DKO compared with Wt mice at 2 hours.Systematic analysis of Nod1/2 DKO mice revealed a possible role of Nod1/2 in the development of renal disease during systemic inflammation.
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam ,  1105 AZ Amsterdam ,  The Netherlands.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Stroo
authors.forename: Loes M
authors.initials: LM
authors.lastname: Butter
authors.forename: Nike
authors.initials: N
authors.lastname: Claessen
authors.forename: Gwen J
authors.initials: GJ
authors.lastname: Teske
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Rubino
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Girardin
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Jaklien C
authors.initials: JC
authors.lastname: Leemans