Phenotypes for Dicer1 Tg(KRT5-cre/PGR)1Der Trp53 MGI:5618123 MGI Mouse

premature death ( J:216813 )

• mean survival is 9 months

• loss of fur by the 5th week of age, with mice nearly devoid of fur and whiskers by 12 weeks of age

abnormal hair shaft morphology ( J:216813 )

abnormal hair follicle morphology ( J:216813 )

• dysmorphic hair follicles with dyskertotic cells in the follicular epithelium

• regions of increased cellularity with many mitotic figures are seen in the interfollicular epidermal layer and above the basal layer

• large amount of DNA damage in the basal layer of follicular epithelium and in the interfollicular epidermis

• there is some evidence of attempts to form new follicles

abnormal hair cycle ( J:216813 )

• at a time when control hair follicles are in the telogen phase of the hair cycles, mutants show anagen growth phase hairs with dysmorphic follicles, abnormal hair shafts, and dyskertotic cells in the follicular epithelium

abnormal epidermis stratum basale morphology ( J:216813 )

• pre-malignant basaloid proliferation is seen

hypergranulosis ( J:216813 )

thick epidermis ( J:216813 )

• increase in thickness of the epidermis with a mean thickness of 51.3 um compared to 24 um in controls

increased skin tumor incidence ( J:216813 )

• mice develop highly aggressive and numerous skin tumors starting at 7-8 months of age with all mice showing skin tumors by 12-15 months of age

• 41% of mice form multiple tumors

increased skin squamous cell carcinoma incidence ( J:216813 )

• mice form moderately or poorly differentiated squamous cell carcinomas and nearly half of mutants develop poorly differentiated carcinomas

• poorly or undifferentiated carcinomas are highly invasive

abnormal skin physiology ( J:216813 )

• the number of apoptotic cells in the epidermis is lower than in single conditional Dicer1 mutants

• increase in the numbers of mitotic cells in the epidermis, indicating increased proliferation