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Homozygous K5Cre transgenic mice have wavy hair and accelerated malignant progression in a murine model of skin carcinogenesis
Molecular carcinogenesis, 2007-01, Vol.46 (1), p.49-59
Chan, Edward L.
Peace, Belinda E.
Toney, Kenya
Kader, Sarah A.
Pathrose, Peterson
Collins, Margaret H.
Waltz, Susan E.
2007
Volltextzugriff (PDF)
Details
Autor(en) / Beteiligte
Chan, Edward L.
Peace, Belinda E.
Toney, Kenya
Kader, Sarah A.
Pathrose, Peterson
Collins, Margaret H.
Waltz, Susan E.
Titel
Homozygous K5Cre transgenic mice have wavy hair and accelerated malignant progression in a murine model of skin carcinogenesis
Ist Teil von
Molecular carcinogenesis, 2007-01, Vol.46 (1), p.49-59
Ort / Verlag
Hoboken: Wiley Subscription Services, Inc., A Wiley Company
Erscheinungsjahr
2007
Quelle
Wiley Blackwell Single Titles
Beschreibungen/Notizen
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.
Sprache
Englisch
Identifikatoren
ISSN: 0899-1987
eISSN: 1098-2744
DOI: 10.1002/mc.20192
Titel-ID: cdi_proquest_miscellaneous_19861899
Format
–
Schlagworte
Alopecia - pathology
,
Animals
,
Carcinogens - toxicity
,
Cell Transformation, Neoplastic
,
Cocarcinogenesis
,
Disease Models, Animal
,
Disease Progression
,
DNA Damage
,
epidermal growth factor receptor (EGFR)
,
Female
,
Genes, ras
,
Genotype
,
Hair - abnormalities
,
Hair Follicle - pathology
,
Homozygote
,
Integrases - metabolism
,
Keratin 5-Cre recombinase (K5Cre)
,
Keratin-15
,
Keratin-5 - genetics
,
Keratin-5 - physiology
,
Keratinocytes - cytology
,
Keratinocytes - metabolism
,
Male
,
malignant progression
,
Mammary Glands, Animal - pathology
,
Mice
,
Mice, Transgenic
,
Papilloma - chemically induced
,
Papilloma - genetics
,
Recombination, Genetic
,
skin carcinogenesis
,
Skin Neoplasms - chemically induced
,
Skin Neoplasms - genetics
,
Tetradecanoylphorbol Acetate - toxicity
,
wavy hair
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