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Homozygous K5Cre transgenic mice have wavy hair and accelerated malignant progression in a murine model of skin carcinogenesis
Author(s) -
Chan Edward L.,
Peace Belinda E.,
Toney Kenya,
Kader Sarah A.,
Pathrose Peterson,
Collins Margaret H.,
Waltz Susan E.
Publication year - 2007
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20192
Subject(s) - biology , carcinogenesis , transgene , genetically modified mouse , cre recombinase , papilloma , lactation , phenotype , ratón , offspring , keratin , gene , endocrinology , congenic , transgenesis , medicine , pathology , genetics , pregnancy , reproductive biology
Mice with conditional gene deletions have been extremely valuable in allowing investigators to study the genes of interest in a tissue‐specific manner. The Cre‐ loxP recombination system provides a powerful tool to produce targeted rearrangements of particular genes. The keratin 5‐Cre recombinase (K5Cre) transgenic mouse line has been used to generate skin specific gene deletions. We found that the K5Cre mice display a unique phenotype when bred to homozygosity. The K5Cre +/+ mice have a wavy hair coat and curly whiskers. Histologically, the hair follicles appear disoriented. Over time, the K5Cre +/+ mice develop patches of alopecia. These mice are also runted when compared to wild‐type controls. Fostering the K5Cre +/+ pups to wild‐type mothers results in normal weight gain, suggesting a maternal defect in milk production. When the K5Cre +/+ mammary glands were examined, we not only found a significant decrease in the number of mammary branches in the virgin females, but also a greater number of quiescent alveoli units in the lactating glands. When the K5Cre +/+ mice were bred to v‐Ha‐ras (Tg · AC) transgenic mice, the resulting Tg · AC +/− K5Cre +/+ offspring were utilized in a chemically induced skin carcinogenesis model. The mice were treated with 2.5 µg of 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) weekly for 10 wk. No difference was observed in the time to onset of papilloma formation, the number of papillomas and the average papilloma volume between the Tg · AC +/− K5Cre +/+ mice and their corresponding controls. Surprisingly, however, the K5Cre +/+ papillomas displayed an accelerated tendency to malignant progression; in addition, the frequency of malignant transformation of the papillomas is significantly enhanced. Although the K5Cre +/+ mice resemble waved‐1 and ‐2 mutants, the molecular basis for the K5Cre +/+ phenotype is probably different. In conclusion, we discovered a unique phenotype associated with the K5Cre +/+ transgenic line. © 2006 Wiley‐Liss, Inc.