Digit tip regrowth and differential gene expression in MRL/Mpj, DBA/2, and C57BL/6 mice


Reprint requests:
Robert B. Chadwick, Musculoskeletal Disease Center, JL Pettis VA Medical Center, Molecular Genetics Division, 11201 Benton Street (151), Loma Linda, CA 92357.
Tel: +909 825 7084 ext. 1582;
Fax: +909 796 1680;
Email: robert.chadwick@med.va.gov


MRL/Mpj mice are the only known strain of mouse that can regenerate cardiac lesions and completely heal ear punches without scarring. This study was undertaken to determine if MRL mice also have greater regrowth capabilities in amputated digit tips. Right paw digit tips of neonatal MRL mice were dissected, with the left front paws as uncut controls. Controls used for regrowth comparison were the DBA/2 and C57BL/6 inbred mouse strains. Consecutive x-ray images were captured of front paws at 0, 7, 14, 21, and 28 days postamputation. MRL mouse digit tips were found to distally regrow more quickly and reform nails partially and completely to a greater degree in comparison with DBA and B6 mice (p<0.05). We next undertook microarray expression analysis to identify the genes involved in digit tip regrowth. Four hundred genes out of 15,000 were significantly differentially expressed (p<0.05) in MRL, DBA, and B6 mice at day 4 in comparison with day 0 control tissue. Multiple differences between MRL, DBA, and B6 strains were found in genes that are implicated in the WNT signaling pathway and transcription. We conclude that MRL mice regrow digits distally more rapidly and partially and completely regrow nails to a greater degree than B6 and DBA strains. This enhanced regrowth is likely due to strain-specific increased expression of genes involved in growth and development.