The MRL.lpr/lpr mouse is known to display gross lymphoproliferative disease and autoimmunity as it ages. This defect is due to a mutation in the fas gene which leads to an inability to mediate apoptosis of lymphocytes. The investigators have noted recently that these animals, as young adults, also display a remarkable capacity for wound healing and regeneration. Specifically, through-and-through ear punches rapidly attain full closure with normal tissue architecture reminiscent of regeneration seen in amphibians as opposed to scarring usually seen in mammals. This phenomenon appears to be regulated by T-cells and is not fas related. In this application, the investigators wish to investigate further the genetics and the immunobiology of this model system. To date, they have: 1) quantitated the gross healing rate difference between the MRL.lpr/lpr mouse and the B6 nonhealing mouse; 2) demonstrated by histology that normal cell growth and microanatomic architecture is completely restored in these animals including blood vessels, hair follicles, and cartilage; 3) confirmed through extensive breeding and backcrossing that there is a multigene genetic basis for this phenomenon; 4) mapped seven healing trait loci at 20 cM resolution to chromosomes 7, 8, 12, 13, and 15; 5) assigned first pass candidate genes which include an interlocking set of signal transduction molecules and morphogen receptors; and 6) have shown that the elimination of alpha +T-cells in these animals regulates this trait.
| Heber-Katz, Ellen; Chen, Pan; Clark, Lise et al. (2004) Regeneration in MRL mice: further genetic loci controlling the ear hole closure trait using MRL and M.m. Castaneus mice. Wound Repair Regen 12:384-92 |
| Gourevitch, Dmitri; Clark, Lise; Chen, Pan et al. (2003) Matrix metalloproteinase activity correlates with blastema formation in the regenerating MRL mouse ear hole model. Dev Dyn 226:377-87 |
| Blankenhorn, Elizabeth P; Troutman, Scott; Clark, Lise Desquenne et al. (2003) Sexually dimorphic genes regulate healing and regeneration in MRL mice. Mamm Genome 14:250-60 |
| Norose, Kazumi; Yano, Akihiko; Zhang, Xiang-Ming et al. (2002) Mapping of genes involved in murine herpes simplex virus keratitis: identification of genes and their modifiers. J Virol 76:3502-10 |
| Leferovich, J M; Bedelbaeva, K; Samulewicz, S et al. (2001) Heart regeneration in adult MRL mice. Proc Natl Acad Sci U S A 98:9830-5 |
| Heber-Katz, E (1999) The regenerating mouse ear. Semin Cell Dev Biol 10:415-9 |
