Phenotypes associated with this allele

• Allele Symbol: Nkx3-1^{tm4(cre/ERT2)Mms}
• Allele Name: targeted mutation 4, Michael M Shen
• Allele ID: MGI:4365630
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Braf^tm1Mmcm/Braf^tm1Mmcm Nkx3-1^tm4(cre/ERT2)Mms/Nkx3-1^+ Pten^tm1Hwu/Pten^+	involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:5543907
cn2	Nkx3-1^tm4(cre/ERT2)Mms/Nkx3-1^+ Pten^tm1Hwu/Pten^tm1Hwu	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6	MGI:4365721

Genotype
MGI:5543907

cn1

• Allelic Composition: Braf^tm1Mmcm/Braf^tm1Mmcm; Nkx3-1^{tm4(cre/ERT2)Mms}/Nkx3-1⁺; Pten^tm1Hwu/Pten⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6

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

mortality/aging

premature death ( J:191327 )

♂ • mutants develop lethal prostate cancer 4 months after tamoxifen induction

neoplasm

increased prostate gland tumor incidence ( J:191327 )

♂ • mutants develop lethal prostate cancer 4 months after tamoxifen induction

♂ • tumors are large and highly proliferative and are primarily composed of luminal epithelial cells

♂ • tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration

♂ • tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative

♂ • treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation

increased prostate gland adenocarcinoma incidence ( J:191327 )

♂ • tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction

increased prostate intraepithelial neoplasia incidence ( J:191327 )

♂ • tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction

increased metastatic potential ( J:191327 )

♂ • metastases to lungs and lymph nodes are seen in tamoxifen treated mutants and disseminated tumor cells are seen in the bone marrow

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:191327 )

♂ • mutants develop lethal prostate cancer 4 months after tamoxifen induction

♂ • tumors are large and highly proliferative and are primarily composed of luminal epithelial cells

♂ • tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration

♂ • tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative

♂ • treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation

increased prostate gland adenocarcinoma incidence ( J:191327 )

♂ • tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction

increased prostate intraepithelial neoplasia incidence ( J:191327 )

♂ • tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction

reproductive system

increased prostate gland tumor incidence ( J:191327 )

♂ • mutants develop lethal prostate cancer 4 months after tamoxifen induction

♂ • tumors are large and highly proliferative and are primarily composed of luminal epithelial cells

♂ • tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration

♂ • tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative

♂ • treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation

increased prostate gland adenocarcinoma incidence ( J:191327 )

♂ • tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction

increased prostate intraepithelial neoplasia incidence ( J:191327 )

♂ • tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction

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:191327

Genotype
MGI:4365721

cn2

• Allelic Composition: Nkx3-1^{tm4(cre/ERT2)Mms}/Nkx3-1⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6

neoplasm

increased prostate gland adenocarcinoma incidence ( J:153425 )

♂ • castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion

increased prostate intraepithelial neoplasia incidence ( J:153425 , J:191327 )

♂ • castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion (J:153425)

♂ • mutants show extensive prostate intraepithelial neoplasia (PIN) III and PIN IV 9-12 months after tamoxifen induction, with some areas of squamous papilloma, however mutants rarely develop lethal prostate cancer up to 2 years following tamoxifen induction (J:191327)

reproductive system

increased prostate gland adenocarcinoma incidence ( J:153425 )

♂ • castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion

increased prostate intraepithelial neoplasia incidence ( J:153425 , J:191327 )

♂ • castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion (J:153425)

♂ • mutants show extensive prostate intraepithelial neoplasia (PIN) III and PIN IV 9-12 months after tamoxifen induction, with some areas of squamous papilloma, however mutants rarely develop lethal prostate cancer up to 2 years following tamoxifen induction (J:191327)

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:153425 )

♂ • castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion

increased prostate intraepithelial neoplasia incidence ( J:153425 , J:191327 )

♂ • castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion (J:153425)

♂ • mutants show extensive prostate intraepithelial neoplasia (PIN) III and PIN IV 9-12 months after tamoxifen induction, with some areas of squamous papilloma, however mutants rarely develop lethal prostate cancer up to 2 years following tamoxifen induction (J:191327)