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

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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 F1 and F2 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 F2 populations. AIRmaxSSshowed higher ear-wound closure than AIRmaxRR 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.

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Acknowledgments

This work was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). The authors dedicate this article to Dr. Guido Biozzi who passed away on 25 December 2006.

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Authors and Affiliations

  1. Laboratório de Imunogenética, Instituto Butantan, São Paulo, Brazil

    Marcelo De Franco, Patrícia dos Santos Carneiro, Luciana Carla Peters, Francisca Vorraro, Andrea Borrego, Orlando Garcia Ribeiro, Nancy Starobinas, Wafa Koury Cabrera & Olga Martinez Ibañez

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  1. Marcelo De Franco
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  2. Patrícia dos Santos Carneiro
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  3. Luciana Carla Peters
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  4. Francisca Vorraro
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  5. Andrea Borrego
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  6. Orlando Garcia Ribeiro
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  7. Nancy Starobinas
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  8. Wafa Koury Cabrera
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  9. Olga Martinez Ibañez
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Correspondence to Marcelo De Franco.

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De Franco, M., Carneiro, P.d.S., Peters, L.C. et al. Slc11a1 (Nramp1) alleles interact with acute inflammation loci to modulate wound-healing traits in mice. Mamm Genome 18, 263–269 (2007). https://doi.org/10.1007/s00335-007-9012-x

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  • DOI: https://doi.org/10.1007/s00335-007-9012-x

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