pigmentation phenotype

• abnormal melanocyte morphology
  • topical administration of 4-hydroxytamoxifen (4-HT) to the ear, tail or flank results in the development of benign melanocytic hyperplasias that are larger and more highly pigmented than in conditional heterozygotes
  (MGI Ref ID J:151023)

mortality/aging

• premature death
  • 7-8 weeks after adenoviral Cre intranasal administration to 6- to 8-week old mutants, treated animals are euthanized because they show labored breathing and general wasting
  (MGI Ref ID J:121715)

normal phenotype

• no abnormal phenotype detected
  • Normal - mice are fertile and born at Mendelian ratios, but no further phenotypic analysis is provided
  (MGI Ref ID J:121715)

respiratory system phenotype

• increased lung adenoma incidence
  • papillary adenomas are detected 6-8 weeks after lower dose adenoviral Cre treatment; lesions seem to increase in size and number
  (MGI Ref ID J:121715)
  • lesions arise in alveolar ducts expanding outward and around broncioles
  (MGI Ref ID J:121715)
  • 7 weeks after high dose Cre treatment, evidence of multiple adenomatous tumor formation is present in mouse lungs, while no tumors are detected in untreated mice after 6 months
  (MGI Ref ID J:121715)
  • after lower dose Cre treatement, adenomas do not grow beyond ~900 um in diameter
  (MGI Ref ID J:121715)
  • at ~14 weeks, papillary adenomas undergo changes at periphery; cells change such that they have more cytoplasm and become eosinophilic
  (MGI Ref ID J:121715)

• increased lung tumor incidence
  • 4 weeks after Cre treatment, mice are treated for 28 days with a pharmacological inhibitor of MEK1/2 which prevents almost all tumor development, while vehicle-treated animals show numerous lung tumors
  (MGI Ref ID J:121715)
  • cellular origins of cancerous are ambiguous aslesions are Clara Cell antigen-negative, but majority of cells express Surfactant protein C as early as 2 weeks after Cre treatment (CCA and SP-C are both markers of alveolar type II pneumocytes)
  (MGI Ref ID J:121715)

• increased lung adenocarcinoma incidence
  • only 2 mice (of 57) that develop adenomas show evidence of progression to adenocarcinoma; cells from these mice display nuclear enlargement, hyperchromasia, and contour irregularities
  (MGI Ref ID J:121715)

• lung epithelium hyperplasia
  • 4 weeks after Cre administration, lung epithelium hyperplasia is observed
  (MGI Ref ID J:121715)
  • at earlier times after Cre treatment, hyperplastic epithelium shows papillary outgrowths, but these were not seen at earlier time points (2-4 weeks post-treatment)
  (MGI Ref ID J:121715)

neoplasm

• increased lung adenocarcinoma incidence
  • only 2 mice (of 57) that develop adenomas show evidence of progression to adenocarcinoma; cells from these mice display nuclear enlargement, hyperchromasia, and contour irregularities
  (MGI Ref ID J:121715)

• increased lung adenoma incidence
  • lesions arise in alveolar ducts expanding outward and around broncioles
  (MGI Ref ID J:121715)
  • after lower dose Cre treatement, adenomas do not grow beyond ~900 um in diameter
  (MGI Ref ID J:121715)
  • at ~14 weeks, papillary adenomas undergo changes at periphery; cells change such that they have more cytoplasm and become eosinophilic
  (MGI Ref ID J:121715)
  • papillary adenomas are detected 6-8 weeks after lower dose adenoviral Cre treatment; lesions seem to increase in size and number
  (MGI Ref ID J:121715)
  • 7 weeks after high dose Cre treatment, evidence of multiple adenomatous tumor formation is present in mouse lungs, while no tumors are detected in untreated mice after 6 months
  (MGI Ref ID J:121715)

• increased lung tumor incidence
  • 4 weeks after Cre treatment, mice are treated for 28 days with a pharmacological inhibitor of MEK1/2 which prevents almost all tumor development, while vehicle-treated animals show numerous lung tumors
  (MGI Ref ID J:121715)
  • cellular origins of cancerous are ambiguous aslesions are Clara Cell antigen-negative, but majority of cells express Surfactant protein C as early as 2 weeks after Cre treatment (CCA and SP-C are both markers of alveolar type II pneumocytes)
  (MGI Ref ID J:121715)

integument phenotype

• skin lesions
  • mice treated with 4-hydroxytamoxifen (4-HT) either topically or systemically develop highly pigmented lesions that are detected by 21-28 days after 4-HT administration; these are small papular pigmented lesions that are not malignant
  (MGI Ref ID J:151023)
  • topical administration of high concentrations of 4-HT occasionally results in periocular lesions on the face and on the glabrous skin of the paws
  (MGI Ref ID J:151023)

pigmentation phenotype

• abnormal melanocyte morphology
  • other melanocytic proliferations form in the dermis with no junctional component in 4-HT treated mice
  (MGI Ref ID J:151023)
  • pigmented lesions in 4-HT treated mice are frequently located at the dermal-epidermal junction with extension into the dermis, indicating melanocytic nevi
  (MGI Ref ID J:151023)

endocrine/exocrine gland phenotype

• increased thyroid carcinoma incidence
  • tumors show both papillary growth morphology and nuclear features of papillary thyroid carcinoma
  (MGI Ref ID J:208854)
  • mice administered tamoxifen develop papillary thyroid carcinomas
  (MGI Ref ID J:208854)
  • even with very long latency, extrathyroidal invasion is not seen and cervical lymph node metastases are not seen
  (MGI Ref ID J:208854)

neoplasm

• increased thyroid carcinoma incidence
  • mice administered tamoxifen develop papillary thyroid carcinomas
  (MGI Ref ID J:208854)
  • tumors show both papillary growth morphology and nuclear features of papillary thyroid carcinoma
  (MGI Ref ID J:208854)
  • even with very long latency, extrathyroidal invasion is not seen and cervical lymph node metastases are not seen
  (MGI Ref ID J:208854)

respiratory system phenotype

• respiratory failure
  • tamoxifen treated mice generally succumb to respiratory compromise due to tracheal compression by large noninvasive tumors
  (MGI Ref ID J:208854)

growth/size/body region phenotype

• enlarged spleen
  • severe hepatosplenomegaly
  (MGI Ref ID J:211690)

• hepatosplenomegaly
  • severe hepatosplenomegaly
  (MGI Ref ID J:211690)

immune system phenotype

• increased dendritic cell number
  • expansion of blood circulating dendritic cell precursors and blood circulating dendritic cells
  (MGI Ref ID J:211690)
  • lesions are associated with massive increase of MHC II+CD11c+ dendritic cells
  (MGI Ref ID J:211690)

• cytokine storm
  • granuloma lesions are associated with an increase in several chemokines and cytokines (Ccl2, Ccl15, Il6, Il10, IFN-gamma, and TGF-beta) indicative of a local cytokine storm
  (MGI Ref ID J:211690)

• granulomatous inflammation
  • histiocytic lesions exhibit classical granulomatous organization, including multinucleated giant cell formation
  (MGI Ref ID J:211690)
  • granuloma lesions contain massive CD11c+ langerin+ infiltrates, a large number of macrophages, NK cells, B cells, and T cells, with a specific accumulation of regulatory T cells
  (MGI Ref ID J:211690)
  • local fibrotic response is seen within the granulomas and surrounding stroma
  (MGI Ref ID J:211690)
  • histiocytic infiltrates in the skin, liver, spleen, and lungs by 8 weeks of age, resulting in a broad destruction of tissue architecture by 16 weeks of age
  (MGI Ref ID J:211690)

• enlarged lymph nodes
  (MGI Ref ID J:211690)

• enlarged spleen
  • severe hepatosplenomegaly
  (MGI Ref ID J:211690)

• hepatosplenomegaly
  • severe hepatosplenomegaly
  (MGI Ref ID J:211690)

• increased inflammatory response
  • mice rapidly develop an aggressive Langerhans-cells histiocytosis-like disease with 100% penetrance
  (MGI Ref ID J:211690)

• abnormal cytokine level
  • granuloma lesions are associated with an increase in several chemokines and cytokines (Ccl2, Ccl15, Il6, Il10, IFN-gamma, and TGF-beta) indicative of a local cytokine storm
  (MGI Ref ID J:211690)

liver/biliary system phenotype

• hepatosplenomegaly
  • severe hepatosplenomegaly
  (MGI Ref ID J:211690)

mortality/aging

• premature death
  • decrease in lifespan
  (MGI Ref ID J:211690)

hematopoietic system phenotype

• anemia
  • severe anemia
  (MGI Ref ID J:211690)

• enlarged spleen
  • severe hepatosplenomegaly
  (MGI Ref ID J:211690)

• hepatosplenomegaly
  • severe hepatosplenomegaly
  (MGI Ref ID J:211690)

• increased dendritic cell number
  • lesions are associated with massive increase of MHC II+CD11c+ dendritic cells
  (MGI Ref ID J:211690)
  • expansion of blood circulating dendritic cell precursors and blood circulating dendritic cells
  (MGI Ref ID J:211690)

homeostasis/metabolism phenotype

• abnormal cytokine level
  • granuloma lesions are associated with an increase in several chemokines and cytokines (Ccl2, Ccl15, Il6, Il10, IFN-gamma, and TGF-beta) indicative of a local cytokine storm
  (MGI Ref ID J:211690)

neoplasm

• increased lung adenoma incidence
  • with induction of Cre expression from the transgene, multiple adenomatous tumors form in mouse lungs
  (MGI Ref ID J:121715)

respiratory system phenotype

• increased lung adenoma incidence
  • with induction of Cre expression from the transgene, multiple adenomatous tumors form in mouse lungs
  (MGI Ref ID J:121715)

endocrine/exocrine gland phenotype

• increased thyroid carcinoma incidence
  • mice with surgical delivery of a cre-expressing adenovirus to the adult thyroid gland develop papillary thyroid carcinoma
  (MGI Ref ID J:208854)

neoplasm

• increased thyroid carcinoma incidence
  • mice with surgical delivery of a cre-expressing adenovirus to the adult thyroid gland develop papillary thyroid carcinoma
  (MGI Ref ID J:208854)

mammalian phenotype

• neoplasm
  • Normal - tamoxifen-treated mice do not develop melanoma
  (MGI Ref ID J:239472)