Phenotypes Associated with This Genotype

Genotype
MGI:5565602

• Allelic Composition: Tg(Pbsn-Fgfr1/Fkbp1a)#aDmsp/0
• Genetic Background: FVB-Tg(Pbsn-Fgfr1/Fkbp1a)#aDmsp

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

neoplasm

increased prostate gland tumor incidence ( J:130340 )

♂ • prostate tumor types that develop following prolonged AP20187 treatment include adenocarcinoma, transitional sarcomatoid-carcinoma, and rare frank sarcoma and show hallmarks of epithelial-to-mesenchymal transition

increased prostate gland adenocarcinoma incidence ( J:130340 )

♂ • 100% of mice develop adenocarcinoma in all prostatic lobes after 42 weeks of treatment with a chemical inducer of dimerization, AP20187

♂ • adenocarcinoma lesions are characterized by presence of invasive hyperchromatic epithelial cells with prominent nucleoli and nuclear atypia along with the formation of multiple small invasive glands within desmoplastic stroma

♂ • maker analysis indicates that tumors are epithelial cell derived and are invasive adenocarcinoma and not neuroendocrine carcinoma

♂ • withdrawal of AP20187 for 20 weeks after 42 weeks of treatment reduces prostate adenocarcinoma progression and cell proliferation, although it does not result in regression

increased prostate intraepithelial neoplasia incidence ( J:87092 , J:130340 )

♂ • mice develop low-grade prostate intraepithelial neoplasia (PIN; type I and II) in the ventral, dorsal-lateral, and anterior prostate after 12 weeks of treatment with a chemical inducer of dimerization, AP20187 (J:87092)

♂ • low-grade PIN is characterized by epithelial piling-up, elongated and hyperchromatic nuclei, and cribiform glandular structures, and stromal thickening in the dorsal lobes of some mice (J:87092)

♂ • by 24 to 30 weeks of AP20187 administration, grade IV PINs are seen, showing extensive dysplastic nuclei, thickened reactive stroma, and herniated acini with extraglandular extension (J:87092)

♂ • withdrawal of AP20187 for 34 weeks after 12 weeks of administration results in PIN reversion (J:130340)

increased metastatic potential ( J:130340 )

♂ • mice that develop sarcomas following prolonged AP20187 treatment show distant metastasis to the liver and lymph nodes

increased sarcoma incidence ( J:130340 )

♂ • after prolonged treatment with AP20187, mice develop rare frank sarcomas which show distant metastasis to the liver and lymph nodes

endocrine/exocrine glands

prostate gland hyperplasia ( J:87092 )

♂ • increase in prostate gland hyperplasia following AP20187 administration

♂ • withdrawal of AP20187 after 4 weeks of treatment reverses the prostate hyperplasia, however withdrawal of AP20187 after 8 weeks of treatment when neovascularization is observed, does not reverse the hyperplasia although further progression to low-grade PIN was not seen

♂ • the increase in prostate gland hyperplasia following AP20187 administration is due to increased proliferation in the prostate gland

increased prostate gland tumor incidence ( J:130340 )

♂ • prostate tumor types that develop following prolonged AP20187 treatment include adenocarcinoma, transitional sarcomatoid-carcinoma, and rare frank sarcoma and show hallmarks of epithelial-to-mesenchymal transition

increased prostate gland adenocarcinoma incidence ( J:130340 )

♂ • 100% of mice develop adenocarcinoma in all prostatic lobes after 42 weeks of treatment with a chemical inducer of dimerization, AP20187

♂ • adenocarcinoma lesions are characterized by presence of invasive hyperchromatic epithelial cells with prominent nucleoli and nuclear atypia along with the formation of multiple small invasive glands within desmoplastic stroma

♂ • maker analysis indicates that tumors are epithelial cell derived and are invasive adenocarcinoma and not neuroendocrine carcinoma

♂ • withdrawal of AP20187 for 20 weeks after 42 weeks of treatment reduces prostate adenocarcinoma progression and cell proliferation, although it does not result in regression

increased prostate intraepithelial neoplasia incidence ( J:87092 , J:130340 )

♂ • mice develop low-grade prostate intraepithelial neoplasia (PIN; type I and II) in the ventral, dorsal-lateral, and anterior prostate after 12 weeks of treatment with a chemical inducer of dimerization, AP20187 (J:87092)

♂ • low-grade PIN is characterized by epithelial piling-up, elongated and hyperchromatic nuclei, and cribiform glandular structures, and stromal thickening in the dorsal lobes of some mice (J:87092)

♂ • by 24 to 30 weeks of AP20187 administration, grade IV PINs are seen, showing extensive dysplastic nuclei, thickened reactive stroma, and herniated acini with extraglandular extension (J:87092)

♂ • withdrawal of AP20187 for 34 weeks after 12 weeks of administration results in PIN reversion (J:130340)

prostate gland cyst ( J:130340 )

♂ • mice develop fluid-filled prostatic cysts after 52 weeks of treatment with a chemical inducer of dimerization, AP20187

reproductive system

prostate gland hyperplasia ( J:87092 )

♂ • increase in prostate gland hyperplasia following AP20187 administration

♂ • withdrawal of AP20187 after 4 weeks of treatment reverses the prostate hyperplasia, however withdrawal of AP20187 after 8 weeks of treatment when neovascularization is observed, does not reverse the hyperplasia although further progression to low-grade PIN was not seen

♂ • the increase in prostate gland hyperplasia following AP20187 administration is due to increased proliferation in the prostate gland

increased prostate gland tumor incidence ( J:130340 )

♂ • prostate tumor types that develop following prolonged AP20187 treatment include adenocarcinoma, transitional sarcomatoid-carcinoma, and rare frank sarcoma and show hallmarks of epithelial-to-mesenchymal transition

increased prostate gland adenocarcinoma incidence ( J:130340 )

♂ • 100% of mice develop adenocarcinoma in all prostatic lobes after 42 weeks of treatment with a chemical inducer of dimerization, AP20187

♂ • adenocarcinoma lesions are characterized by presence of invasive hyperchromatic epithelial cells with prominent nucleoli and nuclear atypia along with the formation of multiple small invasive glands within desmoplastic stroma

♂ • maker analysis indicates that tumors are epithelial cell derived and are invasive adenocarcinoma and not neuroendocrine carcinoma

♂ • withdrawal of AP20187 for 20 weeks after 42 weeks of treatment reduces prostate adenocarcinoma progression and cell proliferation, although it does not result in regression

increased prostate intraepithelial neoplasia incidence ( J:87092 , J:130340 )

♂ • mice develop low-grade prostate intraepithelial neoplasia (PIN; type I and II) in the ventral, dorsal-lateral, and anterior prostate after 12 weeks of treatment with a chemical inducer of dimerization, AP20187 (J:87092)

♂ • low-grade PIN is characterized by epithelial piling-up, elongated and hyperchromatic nuclei, and cribiform glandular structures, and stromal thickening in the dorsal lobes of some mice (J:87092)

♂ • by 24 to 30 weeks of AP20187 administration, grade IV PINs are seen, showing extensive dysplastic nuclei, thickened reactive stroma, and herniated acini with extraglandular extension (J:87092)

♂ • withdrawal of AP20187 for 34 weeks after 12 weeks of administration results in PIN reversion (J:130340)

prostate gland cyst ( J:130340 )

♂ • mice develop fluid-filled prostatic cysts after 52 weeks of treatment with a chemical inducer of dimerization, AP20187

growth/size/body

prostate gland cyst ( J:130340 )

♂ • mice develop fluid-filled prostatic cysts after 52 weeks of treatment with a chemical inducer of dimerization, AP20187

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:130340