Phenotypes Associated with This Genotype

Genotype
MGI:3774672

• Allelic Composition: Tg(KRT14-Snai1)1Efu/0
• Genetic Background: involves: CD-1

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

Tg(KRT14-Snai1)1Efu/0 mice are small, have short tails and flaky skin, and exhibit epidermal hyperproliferation

cellular

decreased sensitivity to induced cell death ( J:229072 )

• keratinocytes are more resistant to chemotoxic stress

increased keratinocyte proliferation ( J:229072 )

• keratinocytes form more and larger colonies than wild-type cells

• treatment of isolated keratinocytes from newborns with 2,4-dimethoxybenzaldehyde (DMBA) results in enhanced proliferation and a survival advantage

• isolated keratinocytes treated with the chemotherapeutic drug doxorubicin show a survival advantage

growth/size/body

decreased body size ( J:97750 )

cachexia ( J:97750 )

• progressively poor health

endocrine/exocrine glands

abnormal sebocyte differentiation ( J:229072 )

• sebaceous gland cells are hyperproliferative and lack terminal differentiation

• in adults, the Mts24+progenitor population that gives rise to the sebaceous gland cells is expanded

• clonogenic potential of Mts24+ progenitor cells is enhanced

sebaceous gland hyperplasia ( J:229072 )

• sebaceous gland cells start to accumulate and several glands per hair follicle are formed, with this disorganization becoming worse over time and leading to sebaceous gland hyperplasia and carcinoma

increased sebaceous gland tumor incidence ( J:229072 )

• 40% incidence of sebaceous gland carcinoma

• sebaceous gland carcinoma is often mixed with squamous cell carcinoma implying an early progenitor population that becomes transformed but still retains some differentiation characteristics

behavior/neurological

decreased food intake ( J:97750 )

• reduction in food intake

neoplasm

increased sebaceous gland tumor incidence ( J:229072 )

• 40% incidence of sebaceous gland carcinoma

• sebaceous gland carcinoma is often mixed with squamous cell carcinoma implying an early progenitor population that becomes transformed but still retains some differentiation characteristics

increased skin tumor incidence ( J:229072 )

• mice start to develop spontaneous skin tumors at 5 months of age, with a median latency of 282 days

• tumors include basal cell carcinoma, squamous cell carcinoma, sebaceous gland carcinoma, and mixed tumors (40%)

increased basal cell carcinoma incidence ( J:229072 )

• 6.67% incidence of basal cell carcinoma

increased skin squamous cell carcinoma incidence ( J:229072 )

• 13.33% incidence of squamous cell carcinoma

increased metastatic potential ( J:229072 )

• sebaceous gland carcinomas are highly metastatic, with draining lymph nodes of 59% of mice with sebaceous gland carcinomas containing carcinoma cells with sebaceous differentiation

• mice show lung metastasis displaying features of terminal skin differentiation in mice with squamous cell carcinoma

limbs/digits/tail

short tail ( J:97750 )

integument

increased keratinocyte proliferation ( J:229072 )

• keratinocytes form more and larger colonies than wild-type cells

• treatment of isolated keratinocytes from newborns with 2,4-dimethoxybenzaldehyde (DMBA) results in enhanced proliferation and a survival advantage

• isolated keratinocytes treated with the chemotherapeutic drug doxorubicin show a survival advantage

abnormal sebocyte differentiation ( J:229072 )

• sebaceous gland cells are hyperproliferative and lack terminal differentiation

• in adults, the Mts24+progenitor population that gives rise to the sebaceous gland cells is expanded

• clonogenic potential of Mts24+ progenitor cells is enhanced

sebaceous gland hyperplasia ( J:229072 )

• sebaceous gland cells start to accumulate and several glands per hair follicle are formed, with this disorganization becoming worse over time and leading to sebaceous gland hyperplasia and carcinoma

increased sebaceous gland tumor incidence ( J:229072 )

• 40% incidence of sebaceous gland carcinoma

• sebaceous gland carcinoma is often mixed with squamous cell carcinoma implying an early progenitor population that becomes transformed but still retains some differentiation characteristics

abnormal epidermal layer morphology ( J:97750 )

• epidermis is hyperproliferative and exhibits differentiation defects

• with age, epidermal folds and undulations develop in the epithelium

thick epidermis ( J:97750 )

abnormal epidermal-dermal junction morphology ( J:97750 )

• adults exhibit alteration of the basement membrane that separates the epidermis from the dermis

flaky skin ( J:97750 )

increased skin tumor incidence ( J:229072 )

• mice start to develop spontaneous skin tumors at 5 months of age, with a median latency of 282 days

• tumors include basal cell carcinoma, squamous cell carcinoma, sebaceous gland carcinoma, and mixed tumors (40%)

increased basal cell carcinoma incidence ( J:229072 )

• 6.67% incidence of basal cell carcinoma

increased skin squamous cell carcinoma incidence ( J:229072 )

• 13.33% incidence of squamous cell carcinoma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
skin cancer		DOID:4159		J:229072