All Phenotypes Pten<tm1Rdp> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Pten^tm1Rdp
targeted mutation 1, Ronald DePinho
MGI:3831201

Summary

9 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Pten^tm1Rdp/Pten^tm1Rdp Smad4^tm1Rdp/Smad4^tm1Rdp Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0	involves: 129 * C57BL/6 * DBA/2	MGI:5431947
cn2	Pten^tm1Rdp/Pten^tm1Rdp Tert^tm3Rdp/Tert^tm3Rdp Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:5431978
cn3	Pten^tm1Rdp/Pten^tm1Rdp Tert^tm1Rdp/Tert^tm1Rdp Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:5431943
cn4	Pten^tm1Rdp/Pten^tm1Rdp Tert^tm1Rdp/Tert⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:5431944
cn5	Pten^tm1Rdp/Pten^tm1Rdp Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:5431945
cn6	Pten^tm1Rdp/Pten⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(GFAP-cre)25Mes/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:3831280
cn7	Braf^tm1Mmcm/Braf⁺ Pten^tm1Rdp/Pten^tm1Rdp Tg(Tyr-cre/ERT2)13Bos/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:5902132
cn8	Pten^tm1Rdp/Pten^tm1Rdp Tg(Tyr-cre/ERT2)13Bos/0	involves: 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:5902135
cn9	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Gt(ROSA)26Sor^{tm1(rtTA,EGFP)Nagy}/Gt(ROSA)26Sor⁺ Pten^tm1Rdp/Pten^tm1Rdp Tg(tetO-BRAF*V600E)29Lc/0 Tg(Tyr-cre/ERT2)13Bos/0	involves: 129/Sv * C57BL/6J * FVB * SJL	MGI:5700641

Allelic Composition	Pten^tm1Rdp/Pten^tm1Rdp Smad4^tm1Rdp/Smad4^tm1Rdp Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129 * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm1Rdp mutation (0 available); any Pten mutation (88 available)
Smad4^tm1Rdp mutation (0 available); any Smad4 mutation (47 available)
Tg(Pbsn-cre)4Prb mutation (2 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (239 available)

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

mortality/aging

premature death ( J:186105 )

• survival time is shorter than in mutant mice wild-type for Smad4

• median survival time of 17.05 weeks

neoplasm

increased prostate gland adenocarcinoma incidence ( J:186105 )

• all develop rapidly progressive, locally invasive prostate adenocarcinomas

• tumors are more aggressive than in mutant mice wild-type for Smad4

increased metastatic potential ( J:186105 )

• bone metastases are seen in some (3 of 24) mice unlike in mutant mice wild-type for Smad4

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:186105 )

• all develop rapidly progressive, locally invasive prostate adenocarcinomas

• tumors are more aggressive than in mutant mice wild-type for Smad4

reproductive system

increased prostate gland adenocarcinoma incidence ( J:186105 )

• all develop rapidly progressive, locally invasive prostate adenocarcinomas

• tumors are more aggressive than in mutant mice wild-type for Smad4

Allelic Composition	Pten^tm1Rdp/Pten^tm1Rdp Tert^tm3Rdp/Tert^tm3Rdp Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm1Rdp mutation (0 available); any Pten mutation (88 available)
Tert^tm3Rdp mutation (0 available); any Tert mutation (55 available)
Tg(Pbsn-cre)4Prb mutation (2 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (239 available)

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

mortality/aging

decreased tumor-free survival time ( J:186105 )

• develop bulky lethal tumors by age 24 weeks of age

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:186105 )

• at generations 3 and 4 (G3/4), all develop invasive prostate adenocarcinomas by 24 weeks of age

increased prostate intraepithelial neoplasia incidence ( J:186105 )

• at G3/4, high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age

neoplasm

increased prostate gland adenocarcinoma incidence ( J:186105 )

• at generations 3 and 4 (G3/4), all develop invasive prostate adenocarcinomas by 24 weeks of age

increased prostate intraepithelial neoplasia incidence ( J:186105 )

• at G3/4, high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age

increased metastatic potential ( J:186105 )

• in some (5 of 20) G3/4 mice lumbar spine metastases are seen unlike in G0 mice

reproductive system

increased prostate gland adenocarcinoma incidence ( J:186105 )

• at generations 3 and 4 (G3/4), all develop invasive prostate adenocarcinomas by 24 weeks of age

increased prostate intraepithelial neoplasia incidence ( J:186105 )

• at G3/4, high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age

cellular

abnormal chromosome morphology ( J:186105 )

• increase in the number of chromosomal aberrations in tumor cells from G3/4 mice compared to G0 mice

increased telomere length ( J:186105 )

• increased length in prostate tumor cells compared to G3/4 mice homozygous for Tert^tm1Rdp, Pten^tm1Rdp and Trp53^tm1Brn and hemizygous for Tg(Pbsn-cre)4Prb

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:186105

Allelic Composition	Pten^tm1Rdp/Pten^tm1Rdp Tert^tm1Rdp/Tert^tm1Rdp Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm1Rdp mutation (0 available); any Pten mutation (88 available)
Tert^tm1Rdp mutation (0 available); any Tert mutation (55 available)
Tg(Pbsn-cre)4Prb mutation (2 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (239 available)

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

neoplasm

increased prostate intraepithelial neoplasia incidence ( J:186105 )

• at generations 3 and 4 (G3/4), all mice develop smaller, poorly progressive tumors compared to G0 mice

• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age

• most tumors fail to progress beyond HPIN by 24 weeks of age unlike in G0 mice

decreased tumor growth/size ( J:186105 )

• smaller, poorly progressive tumors compared to tumors in G0 mice

• markedly increased apoptosis and decreased proliferation in tumor cells compared tumor cells from G0 mice

endocrine/exocrine glands

increased prostate intraepithelial neoplasia incidence ( J:186105 )

• at generations 3 and 4 (G3/4), all mice develop smaller, poorly progressive tumors compared to G0 mice

• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age

• most tumors fail to progress beyond HPIN by 24 weeks of age unlike in G0 mice

cellular

decreased telomere length ( J:186105 )

• reduced at G3/4

reproductive system

increased prostate intraepithelial neoplasia incidence ( J:186105 )

• at generations 3 and 4 (G3/4), all mice develop smaller, poorly progressive tumors compared to G0 mice

• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age

• most tumors fail to progress beyond HPIN by 24 weeks of age unlike in G0 mice

Allelic Composition	Pten^tm1Rdp/Pten^tm1Rdp Tert^tm1Rdp/Tert⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * DBA/2

Find Mice

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

mortality/aging

premature death ( J:186105 )

neoplasm

increased prostate gland adenocarcinoma incidence ( J:186105 )

• all develop rapidly progressive, locally invasive prostate adenocarcinomas

increased prostate intraepithelial neoplasia incidence ( J:186105 )

• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age

reproductive system

increased prostate gland adenocarcinoma incidence ( J:186105 )

• all develop rapidly progressive, locally invasive prostate adenocarcinomas

increased prostate intraepithelial neoplasia incidence ( J:186105 )

• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:186105 )

• all develop rapidly progressive, locally invasive prostate adenocarcinomas

increased prostate intraepithelial neoplasia incidence ( J:186105 )

• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age

Allelic Composition	Pten^tm1Rdp/Pten^tm1Rdp Trp53^tm1Brn/Trp53^tm1Brn Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm1Rdp mutation (0 available); any Pten mutation (88 available)
Tg(Pbsn-cre)4Prb mutation (2 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (239 available)

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

mortality/aging

premature death ( J:186105 )

• median survival time of 26.3 weeks

neoplasm

increased prostate gland adenocarcinoma incidence ( J:186105 )

• all develop rapidly progressive, locally invasive prostate adenocarcinomas

increased prostate intraepithelial neoplasia incidence ( J:186105 )

• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age

reproductive system

increased prostate gland adenocarcinoma incidence ( J:186105 )

• all develop rapidly progressive, locally invasive prostate adenocarcinomas

increased prostate intraepithelial neoplasia incidence ( J:186105 )

• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:186105 )

• all develop rapidly progressive, locally invasive prostate adenocarcinomas

increased prostate intraepithelial neoplasia incidence ( J:186105 )

• high-grade prostate intraepithelial neoplasia (HPIN) in all mice by 9 weeks of age

Allelic Composition	Pten^tm1Rdp/Pten⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(GFAP-cre)25Mes/0
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm1Rdp mutation (0 available); any Pten mutation (88 available)
Tg(GFAP-cre)25Mes mutation (2 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (239 available)

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

behavior/neurological

ataxia ( J:140704 )

• in 73% of mice at 15 to 40 weeks of age

paralysis ( J:140704 )

• in 73% of mice at 15 to 40 weeks of age

seizures ( J:140704 )

• in 73% of mice at 15 to 40 weeks of age

neoplasm

increased glioma incidence ( J:140704 )

• 73% of mice develop malignant gliomas consisting of anaplastic astrocytomas (in 66% of mice with tumors) and glioblastomas (in 34% of mice with tumors)

increased glioblastoma incidence ( J:140704 )

• 34% of mice with tumors develop glioblastomas

increased astrocytoma incidence ( J:140704 )

• anaplastic astrocytomas (in 66% of mice with tumors)

nervous system

seizures ( J:140704 )

• in 73% of mice at 15 to 40 weeks of age

increased glioma incidence ( J:140704 )

• 73% of mice develop malignant gliomas consisting of anaplastic astrocytomas (in 66% of mice with tumors) and glioblastomas (in 34% of mice with tumors)

increased glioblastoma incidence ( J:140704 )

• 34% of mice with tumors develop glioblastomas

increased astrocytoma incidence ( J:140704 )

• anaplastic astrocytomas (in 66% of mice with tumors)

Allelic Composition	Braf^tm1Mmcm/Braf⁺ Pten^tm1Rdp/Pten^tm1Rdp Tg(Tyr-cre/ERT2)13Bos/0
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Braf^tm1Mmcm mutation (3 available); any Braf mutation (60 available)
Pten^tm1Rdp mutation (0 available); any Pten mutation (88 available)
Tg(Tyr-cre/ERT2)13Bos mutation (12 available)

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

integument

increased cutaneous melanoma incidence ( J:151023 )

• 7-10 days following 4-hydroxytamoxifen (4-HT) treatment, all mice show expansion of highly pigmented cells that develop into pigmented malignant lesions in locations of 4-HT administration such as the face, flank, or tail skin

• pigmented melanoma cells are seen throughout the dermis and subcutis of 4-HT treated mice and show pagetoid spread into the epidermis

• lesions in 4-HT treated mice progress rapidly to advanced malignancy such that all mice require euthanasia 25-50 days following 4-HT administration

• treatment of 4-HT treated mice with the MEK1/2 inhibitor PD325901 or the mTorc1 inhibitor rapamycin inhibits melanoma formation

• mice in which drug treatment is ceased subsequently develop malignant melanoma

• mice treated once with PD325901 to prevent melanoma remain sensitive to the anti-melanoma action of a second round of PD325901 administration

• treatment of melanoma bearing mice with either PD325901 or rapamycin inhibits further tumor growth but has little or no effect on tumor regression

• treatment of melanoma bearing with both PD325901 or rapamycin results in a 20% reduction in tumor size

neoplasm

increased cutaneous melanoma incidence ( J:151023 )

• pigmented melanoma cells are seen throughout the dermis and subcutis of 4-HT treated mice and show pagetoid spread into the epidermis

• lesions in 4-HT treated mice progress rapidly to advanced malignancy such that all mice require euthanasia 25-50 days following 4-HT administration

• treatment of 4-HT treated mice with the MEK1/2 inhibitor PD325901 or the mTorc1 inhibitor rapamycin inhibits melanoma formation

• mice in which drug treatment is ceased subsequently develop malignant melanoma

• mice treated once with PD325901 to prevent melanoma remain sensitive to the anti-melanoma action of a second round of PD325901 administration

• treatment of melanoma bearing mice with either PD325901 or rapamycin inhibits further tumor growth but has little or no effect on tumor regression

• treatment of melanoma bearing with both PD325901 or rapamycin results in a 20% reduction in tumor size

increased metastatic potential ( J:151023 )

• spread of melanoma is seen into the regional draining lymph nodes in 100% of mice and to the lungs in some cases

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
skin melanoma		DOID:8923	OMIM:608035 OMIM:612263	J:151023

Allelic Composition	Pten^tm1Rdp/Pten^tm1Rdp Tg(Tyr-cre/ERT2)13Bos/0
Genetic Background	involves: 129S6/SvEvTac * C57BL/6 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm1Rdp mutation (0 available); any Pten mutation (88 available)
Tg(Tyr-cre/ERT2)13Bos mutation (12 available)

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

pigmentation

pigmentation phenotype ( J:151023 )

N	• mice treated with 4-hydroxytamoxifen do not show any melanocytic phenotype over 18 months

Allelic Composition	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Gt(ROSA)26Sor^{tm1(rtTA,EGFP)Nagy}/Gt(ROSA)26Sor⁺ Pten^tm1Rdp/Pten^tm1Rdp Tg(tetO-BRAF*V600E)29Lc/0 Tg(Tyr-cre/ERT2)13Bos/0
Genetic Background	involves: 129/Sv * C57BL/6J * FVB * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn2a^tm1Rdp mutation (6 available); any Cdkn2a mutation (67 available)
Gt(ROSA)26Sor^{tm1(rtTA,EGFP)Nagy} mutation (5 available); any Gt(ROSA)26Sor mutation (992 available)
Pten^tm1Rdp mutation (0 available); any Pten mutation (88 available)
Tg(tetO-BRAF*V600E)29Lc mutation (0 available)
Tg(Tyr-cre/ERT2)13Bos mutation (12 available)

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

neoplasm

increased melanoma incidence ( J:221902 )

• tamoxifen treated mice administered doxycycline in the diet develop melanoma with a median latency of 60 days and with 85% penetrance

• withdrawal of doxycycline leads to rapid tumor regression

• treatment with PLX4720 BRAF inhibitor results in tumor growth inhibition in mutants, however, after continual administration of this inhibitor, mice develop drug resistance

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