Phenotypes Associated with This Genotype

Genotype
MGI:5487550

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tgfbr1^tm1.1Karl/Tgfbr1^tm1.1Karl; Tg(KRT14-cre/ERT)20Efu/0
• Genetic Background: involves: 129 * 129S4/SvJae * C57BL/6 * CD-1 * FVB/N

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

Tgfbr1^tm1.1Karl/Tgfbr1^tm1.1Karl Pten^tm1Hwu/Pten^tm1Hwu Tg(KRT14-cre/ERT)20Efu/0 mice develop anal squamous cell carcinoma

neoplasm

increased squamous cell carcinoma incidence ( J:194652 , J:209026 )

• tamoxifen treated mutants to induce cre-mediated deletion of Tgfbr1 and Pten develop head and neck tumors; papillomas progress to squamous cell carcinoma in the head and neck and oral cavity (J:194652)

• treatment with rapamycin 2 weeks after tamoxifen administration delays initiation and reduces progression of papilloma and onset of squamous cell carcinoma (J:194652)

• rapamycin treatment of mice with already established head and neck squamous cell carcinoma results in regression of those tumors; rapamycin decreases cell proliferation and increases apoptosis in these tumors (J:194652)

• anal neoplasms that develop in tamoxifen treated mice originate from squamous epithelia and not from columnar epithelia, indicating squamous cell carcinoma (J:209026)

• invasion into adjacent muscle tissue is seen in some mice (J:209026)

• anal squamous cell carcinoma shows increased levels of proinflammatory cytokines (J:209026)

• all mice develop head and neck squamous cell carcinomas 16 weeks after tamoxifen induction (J:209026)

• rapamycin treatment 2 weeks after tamoxifen administration decreases cell proliferation, and delays and reduces the progression of anal squamous cell carcinoma (J:209026)

increased papilloma incidence ( J:194652 )

• tamoxifen treated mutants to induce cre-mediated deletion of Tgfbr1 and Pten develop head and neck and oral cavity papillomas that progress to squamous cell carcinoma

increased organ/body region tumor incidence ( J:209026 )

• 33% of mice develop visible anal tumors in 6 weeks after tamoxifen treatment

increased oral papilloma incidence ( J:194652 )

digestive/alimentary system

abnormal anal canal morphology ( J:209026 )

• 4 weeks after oral tamoxifen treatment for 5 consecutive days, hyperplasia is seen in the perianal areas

growth/size/body

increased oral papilloma incidence ( J:194652 )

craniofacial

increased oral papilloma incidence ( J:194652 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
anal canal carcinoma		DOID:6126	OMIM:105580	J:209026
head and neck squamous cell carcinoma		DOID:5520	OMIM:275355	J:194652