Genetic analysis of ultraviolet radiation-induced skin hyperplasia and neoplasia in a laboratory marsupial model (Monodelphis domestica).

Abstract

Monodelphis domestica, the laboratory opossum, develops hyperplasia and neoplasia of shaved skin after repeated exposure to ultraviolet radiation (UVR). We exposed Monodelphis from genetically diverse families within our colony to determine whether there are any heritable components to the risk of two distinct skin lesion phenotypes-melanocytic nevus (MN) and advanced hyperkeratosis (HK). From about 5 months of age, animals were shaved and exposed three times a week to a dose of about 125 J/m2 of UVR (spectral peak, 302 nm; range, 280-400 nm). Of 33 sibships (151 individuals) that completed at least 30 weeks of the protocol, 137 completed 45 weeks. For genetic analyses, each animal was classified at 30 and 45 weeks as affected with MN and HK or not affected. Heritabilities were estimated using a variance decomposition approach. Susceptibility to MN showed no significant evidence for a genetic component at 30 or 45 weeks. In sharp contrast, susceptibility to HK was under virtually complete genetic control (heritability, 0.999; P < 0.001) at 30 weeks, and had a moderately high heritability (0.702; P < 0.001) at 45 weeks. We conclude that this model has great potential for identifying genes that confer susceptibility to UVR-induced skin lesions and for investigating environmental factors that may contribute to the increasing incidence of skin cancer in human populations.