Slc11a1 (Nramp1) alleles interact with acute inflammation loci to modulate wound-healing traits in mice.
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.
De Franco
Marcelo
M
Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil. mdfranco@butantan.gov.br
Carneiro
Patrícia dos Santos
Pdos S
Peters
Luciana Carla
LC
Vorraro
Francisca
F
Borrego
Andrea
A
Ribeiro
Orlando Garcia
OG
Starobinas
Nancy
N
Cabrera
Wafa Koury
WK
Ibañez
Olga Martinez
OM
D000483:Alleles; D000818:Animals; D027682:Cation Transport Proteins / Q000235:genetics*; D003433:Crosses, Genetic; D005260:Female; D005819:Genetic Markers; D007249:Inflammation / Q000235:genetics*; D008297:Male; D051379:Mice; D040641:Quantitative Trait Loci / Q000235:genetics; D019655:Quantitative Trait, Heritable; D013997:Time Factors; D014945:Wound Healing / Q000235:genetics*; D000099173:Natural Resistance-associated Macrophage Protein 1
D027682:Cation Transport Proteins; D005819:Genetic Markers; D000099173:Natural Resistance-associated Macrophage Protein 1