Slc11a1 (Nramp1) alleles interact with acute inflammation loci to modulate wound-healing traits in mice

Abstract

Lines of mice were obtained by selective breeding for maximum (AIRmax) or minimum (AIRmin) acute inflammation. They present distinct neutrophil influx and show frequency disequilibrium of the solute carrier family 11a member 1 (Slc11a1) alleles. This gene is involved in ion transport at the endosomes within macrophages and neutrophils, interfering in their activation. Homozygous AIRmax and AIRmin sublines for the Slc11a1 gene were produced to examine the interaction of this gene with the acute inflammatory loci. The present work investigated wound-healing traits in AIRmax and AIRmin mice, in F(1) and F(2) intercrosses, and in Slc11a1 sublines. Two-millimeter ear punches were made in the mice and hole closure was measured during 40 days. AIRmax mice demonstrated significant tissue repair while AIRmin mice did not. Significant differences between the responses of male and female mice were also observed. Wound-healing traits demonstrated a correlation with neutrophil influx in F(2) populations. AIRmax( SS )showed higher ear-wound closure than AIRmax( RR ) mice, suggesting that the Slc11a1 S allele favored ear tissue repair. QTL analysis has detected two inflammatory loci modulating ear wound healing on chromosomes 1 and 14. These results suggest the involvement of the acute inflammation modifier QTL in the wound-healing phenotype.

Genetic Control of IL-1β Production and Inflammatory Response by the Mouse Irm1 Locus

“…2) informatics.jax.org). Previous studies by our group showed that AIRmax and AIRmin differ in the susceptibility to pristaneinduced arthritis (18), to lung and skin chemical carcinogenesis (17,19), and to wound-healing capacity and tissue repair (20). Thus, it is plausible that the same candidate gene(s) in the Irm1 locus regulates all or several of these related responses.…”

Unexpected Regeneration in Middle-Aged Mice

“…One geneticist estimates that the time from removing the mouse from its cage to returning it is approximately 20 sec. 10,11 The need for multiple measurements has never been explained explicitly, but seems designed to control for various sources of variability, such as mouse movement, tissue movement (i.e., "play") due to the hole being in the very curved center of the mouse ear, and observer imprecision. Of particular concern is the fact that greater accuracy is achieved only by increasing periods of restraint, which can lead to restraint stress and cortisol excess.…”

A new model of outbred genetically selected mice which present a strong acute inflammatory response in the absence of complement component C5

“…In a previous study, we demonstrated that homozygous Slc11a1 SS AIRmax mice present a mild reduction in neutrophil infiltration [10] and more rapid skin wound healing than that observed in AIRmax Slc11a1 RR (C5 deficient) mice [27]. The C5 deficient mouse strain B10D2oSn-J presented a similar delay in liver regeneration [12] after CCl4-induced liver damage when compared to C5 sufficient mice (B10D2nSn-J).…”