All Phenotypes Pten<tm2.1Ppp> MGI Mouse

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Phenotypes associated with this allele

Allele Symbol
Allele Name
Allele ID

Pten^tm2.1Ppp
targeted mutation 2.1, Pier Paolo Pandolfi
MGI:2679886

Summary

30 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Pten^tm2.1Ppp/Pten^tm2.1Ppp	involves: 129S1/Sv	MGI:5320164
cn2	Kras^tm4Tyj/Kras⁺ Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0	129.Cg-Kras^tm4Tyj Tg(Tpo-cre)1Shk Pten^tm2.1Ppp	MGI:5897668
cn3	Pten^tm2.1Ppp/Pten^tm2.1Ppp Trp53^tm1Brn/Trp53^tm1Brn Tg(TPO-cre)1Shk/0	129.Cg-Tg(TPO-cre)1Shk Trp53^tm1Brn Pten^tm2.1Ppp	MGI:5897837
cn4	Cdkn1b^tm1Ako/Cdkn1b⁺ Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0	129S1.Cg-Cdkn1b^tm1Ako Tg(TPO-cre)1Shk Pten^tm2.1Ppp	MGI:4838319
cn5	Cdkn1b^tm1Ako/Cdkn1b^tm1Ako Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0	129S1.Cg-Cdkn1b^tm1Ako Tg(TPO-cre)1Shk Pten^tm2.1Ppp	MGI:4838318
cn6	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0	129S1.Cg-Pten^tm2.1Ppp Tg(TPO-cre)1Shk	MGI:4838317
cn7	Gt(ROSA)26Sor^{tm1(CAG-MYCN,-luc)Jhsc}/Gt(ROSA)26Sor⁺ Pten^tm2.1Ppp/Pten^tm2.1Ppp Rb1^tm2Brn/Rb1⁺ Tg(Pbsn-cre)4Prb/0	involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:7277820
cn8	Gt(ROSA)26Sor^{tm1(CAG-MYCN,-luc)Jhsc}/Gt(ROSA)26Sor⁺ Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb/0	involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:7277821
cn9	Pten^tm2.1Ppp/Pten^tm2.1Ppp Rb1^tm2Brn/Rb1^tm2Brn Tg(Pbsn-cre)4Prb/0	involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:7277828
cn10	Gt(ROSA)26Sor^{tm1(CAG-MYCN,-luc)Jhsc}/Gt(ROSA)26Sor⁺ Pten^tm2.1Ppp/Pten^tm2.1Ppp Rb1^tm2Brn/Rb1^tm2Brn Tg(Pbsn-cre)4Prb/0	involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:7277819
cn11	Pik3cd^tm1Tnr/Pik3cd^tm1Tnr Pten^tm2.1Ppp/Pten^tm2.1Ppp Cd19^tm1(cre)Cgn/Cd19⁺	involves: 129P2/OlaHsd * 129S1/Sv * 129S4/SvJae * C57BL/6	MGI:3796508
cn12	Pten^tm2.1Ppp/Pten⁺ Spry1^tm1Jdli/Spry1^tm1.1Jdli Spry2^tm1Mrt/Spry2^tm1.1Mrt Tg(Osr1-cre)4Mrt/0	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * FVB/N	MGI:5467305
cn13	Braf^tm1Mmcm/Braf⁺ Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Tyr-cre/ERT2)13Bos/0	involves: 129P2/OlaHsd * 129S1/Sv * FVB	MGI:5902129
cn14	Braf^tm1Mmcm/Braf⁺ Pten^tm2.1Ppp/Pten⁺ Tg(Tyr-cre/ERT2)13Bos/0	involves: 129P2/OlaHsd * 129S1/Sv * FVB	MGI:5902136
cn15	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(CAG-Bgeo,-Spry2,-ALPP)1Mrt/0 Tg(Osr1-cre)4Mrt/0	involves: 129P2/OlaHsd * 129S1/Sv * FVB/N	MGI:5467306
cn16	Hras^tm1Jaf/Hras^tm1Jaf Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0	involves: 129S1/Sv * 129S6/SvEvTac * FVB/NCr	MGI:5784778
cn17	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tnfrsf4^tm2(cre)Nik/Tnfrsf4⁺	involves: 129S1/Sv * 129X1/SvJ	MGI:4850096
cn18	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Osr1-cre)4Mrt/0	involves: 129S1/Sv * 129X1/SvJ	MGI:5467307
cn19	Eif4e^tm1.1Lfur/Eif4e^tm1.1Lfur Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2	MGI:4830313
cn20	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)8113ANg/0	involves: 129S1/Sv * C57BL/6	MGI:2679902
cn21	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(GFAP-TAg121)1Tvd/0	involves: 129S1/Sv * C57BL/6 * C57BL/6J * DBA/2 * FVB/N	MGI:5286094
cn22	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb/0	involves: 129S1/Sv * C57BL/6 * DBA/2	MGI:2679901
cn23	Pten^tm2.1Ppp/Pten^tm2.1Ppp Trp53^tm1Thl/Trp53^tm1Thl Tg(Pbsn-cre)4Prb/0	involves: 129S1/Sv * C57BL/6 * DBA/2	MGI:3603330
cn24	Gt(ROSA)26Sor^{tm1(TMPRSS2/ERG)Key}/Gt(ROSA)26Sor^{tm1(TMPRSS2/ERG)Key} Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb/0	involves: 129S1/Sv * C57BL/6 * DBA/2	MGI:5524280
cn25	Gt(ROSA)26Sor^{tm1(SPOP*F133V)Mrbn}/Gt(ROSA)26Sor⁺ Pten^tm2.1Ppp/Pten⁺ Tg(Pbsn-cre)4Prb/0	involves: 129S1/Sv * C57BL/6 * DBA/2	MGI:6275174
cn26	Gt(ROSA)26Sor^{tm1(SPOP*F133V)Mrbn}/Gt(ROSA)26Sor⁺ Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb/0	involves: 129S1/Sv * C57BL/6 * DBA/2	MGI:6275175
cn27	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Dhh-cre)1Mejr/0	involves: 129S1/Sv * C57BL/6 * FVB/N * SJL	MGI:5485416
cn28	Pten^tm2.1Ppp/Pten⁺ Tg(Cnp-EGFR)10Nrat/0 Tg(Dhh-cre)1Mejr/0	involves: 129S1/Sv * C57BL/6 * FVB/N * SJL	MGI:5485415
cn29	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Cnp-EGFR)10Nrat/0 Tg(Dhh-cre)1Mejr/0	involves: 129S1/Sv * C57BL/6 * FVB/N * SJL	MGI:5485414
cn30	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Tyr-cre/ERT2)13Bos/0	involves: 129S1/Sv * FVB	MGI:5902133

Allelic Composition	Pten^tm2.1Ppp/Pten^tm2.1Ppp
Genetic Background	involves: 129S1/Sv

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)

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

nervous system

abnormal dendrite morphology ( J:181347 )

• mice injected with an adenovirus expressing Cre recombinase into the left auditory cortex exhibit neurons with increased dendritic total length and branch number

increased dendritic spine density ( J:181347 )

• mice injected with an adenovirus expressing Cre recombinase into the left auditory cortex exhibit neurons with increased density of dendritic spines

abnormal synaptic transmission ( J:181347 )

• mice injected with an adenovirus expressing Cre recombinase into the left auditory cortex have neurons that exhibit lower input resistance than nearby control neurons without adenovirus

• pyramidal neurons from mice injected with an adenovirus expressing Cre recombinase into the left auditory cortex receive stronger local inputs in the auditory cortex than control neurons without adenovirus; the increase is greatest for inputs arising from layer 2 but is present in all layers

abnormal excitatory postsynaptic currents ( J:181347 )

• neurons from mice injected with an adenovirus expressing Cre recombinase into the left auditory cortex or the left auditory thalamus exhibit increased neuronal responses to auditory callosal and thalamic inputs as indicated by enhanced light-evoked EPSCs after channelrhodopsin-2 adenoviral expression (which allows for neurons to be excited to fire action potentials by flashing blue light)

abnormal miniature excitatory postsynaptic currents ( J:181347 )

• mice injected with an adenovirus expressing Cre recombinase into the left auditory cortex exhibit increased miniature spontaneous EPSC frequency and miniature EPSC amplitude

increased miniature excitatory postsynaptic current amplitude ( J:181347 )

• in mice injected with an adenovirus expressing Cre recombinase into the left auditory cortex

increased miniature excitatory postsynaptic current frequency ( J:181347 )

• in mice injected with an adenovirus expressing Cre recombinase into the left auditory cortex

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:181347

Allelic Composition	Kras^tm4Tyj/Kras⁺ Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0
Genetic Background	129.Cg-Kras^tm4Tyj Tg(Tpo-cre)1Shk Pten^tm2.1Ppp

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kras^tm4Tyj mutation (9 available); any Kras mutation (84 available)
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(TPO-cre)1Shk mutation (1 available)

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

mortality/aging

premature death ( J:147732 )

• 50% of mice die within 7 weeks from birth and none survive over 4 months of age

• treatment with LY294002, an inhibitor of PI3K, twice a week starting at 3 weeks of age prolongs survival of mice

endocrine/exocrine glands

enlarged thyroid gland ( J:147732 )

• mice develop thyroids 200- to 500-fold larger than controls

increased thyroid carcinoma incidence ( J:147732 )

• mice rapidly develop thyroid follicular carcinomas

• 30-90% of the thyroid glands are replaced by microfollicular to solid areas, indicating thyroid follicular cancer, including capsular, muscle, and vascular invasion

homeostasis/metabolism

increased thyroxine level ( J:147732 )

decreased circulating thyroid-stimulating hormone level ( J:147732 )

neoplasm

increased thyroid carcinoma incidence ( J:147732 )

• mice rapidly develop thyroid follicular carcinomas

• 30-90% of the thyroid glands are replaced by microfollicular to solid areas, indicating thyroid follicular cancer, including capsular, muscle, and vascular invasion

increased metastatic potential ( J:147732 )

• all mice surviving at least 12 weeks develop thyroglobulin-positive lung metastases

Allelic Composition	Pten^tm2.1Ppp/Pten^tm2.1Ppp Trp53^tm1Brn/Trp53^tm1Brn Tg(TPO-cre)1Shk/0
Genetic Background	129.Cg-Tg(TPO-cre)1Shk Trp53^tm1Brn Pten^tm2.1Ppp

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(TPO-cre)1Shk mutation (1 available)
Trp53^tm1Brn mutation (18 available); any Trp53 mutation (240 available)

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

mortality/aging

premature death ( J:211100 )

• median survival is 38.4 weeks

neoplasm

increased thyroid carcinoma incidence ( J:211100 )

• 4-8 week old mice only show areas of well differentiated follicular carcinomas but go on to develop well-differentiated follicular carcinomas by 8-10 months of age exhibiting spindle cell morphology, giant, osteoclast-like, multinucleated cells and areas of osseous metaplasia resembling human thyroid anaplastic carcinomas

• anaplastic thyroid carcinomas undergo dedifferentiation, genomic instability and epithelial-to-mesenchymal transition and exhibit a shift from an oxidative to a glycolytic pathway

increased metastatic potential ( J:211100 )

• aggressive tumors invade locally into the muscle and trachea and metastasize to the lungs in 28% of mice, or less often, to the liver

endocrine/exocrine glands

enlarged thyroid gland ( J:211100 )

• all 8-10 month old mice exhibit enlarged thyroid gland causing severe tracheal compression

increased thyroid carcinoma incidence ( J:211100 )

• anaplastic thyroid carcinomas undergo dedifferentiation, genomic instability and epithelial-to-mesenchymal transition and exhibit a shift from an oxidative to a glycolytic pathway

homeostasis/metabolism

decreased thyroid-stimulating hormone level ( J:211100 )

• reduction in TSH serum levels

• however, T4 levels are normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thyroid gland carcinoma		DOID:3963		J:211100

Allelic Composition	Cdkn1b^tm1Ako/Cdkn1b⁺ Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0
Genetic Background	129S1.Cg-Cdkn1b^tm1Ako Tg(TPO-cre)1Shk Pten^tm2.1Ppp

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1b^tm1Ako mutation (0 available); any Cdkn1b mutation (26 available)
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(TPO-cre)1Shk mutation (1 available)

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

mortality/aging

premature death ( J:165293 )

• mean survival is 58 weeks of age

neoplasm

increased thyroid adenoma incidence ( J:165293 )

• no gender differences in development of adenomas

increased thyroid carcinoma incidence ( J:165293 )

• no gender differences in development of carcinomas

endocrine/exocrine glands

increased thyroid adenoma incidence ( J:165293 )

• no gender differences in development of adenomas

increased thyroid carcinoma incidence ( J:165293 )

• no gender differences in development of carcinomas

Allelic Composition	Cdkn1b^tm1Ako/Cdkn1b^tm1Ako Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0
Genetic Background	129S1.Cg-Cdkn1b^tm1Ako Tg(TPO-cre)1Shk Pten^tm2.1Ppp

Find Mice

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

mortality/aging

premature death ( J:165293 )

• mean survival is 21 weeks and all mutants die by 6 months of age

endocrine/exocrine glands

thyroid gland hyperplasia ( J:165293 )

respiratory system

respiratory distress ( J:165293 )

• hyperplastic thyroids cause dyspnea and prevent feeding

Allelic Composition	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0
Genetic Background	129S1.Cg-Pten^tm2.1Ppp Tg(TPO-cre)1Shk

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(TPO-cre)1Shk mutation (1 available)

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

mortality/aging

premature death ( J:165293 )

• females have a reduced lifespan compared to males, with a mean survival age of 73 weeks compared to 83 weeks in males

• mutants start to show signs of illness starting after 1 year of age

endocrine/exocrine glands

thyroid gland hyperplasia ( J:165293 )

• enlarged thyroid

• ovariectomization of females results in reduced proliferative index of thyroids to a similar level seen in males

increased thyroid adenoma incidence ( J:165293 )

• 52% of females develop thyroid follicular adenomas between 8-12 months of age compared to 12% of males

increased thyroid carcinoma incidence ( J:165293 )

• 50% of the females and 35% of males over one year of age develop invasive and often metastatic thyroid follicular carcinomas

homeostasis/metabolism

increased thyroxine level ( J:165293 )

• thyroxine levels are slightly, but significantly, increased in all mice with adenomas

decreased thyroid-stimulating hormone level ( J:165293 )

• aging mice exhibit suppression of thyroid-stimulating hormone

neoplasm

increased thyroid adenoma incidence ( J:165293 )

• 52% of females develop thyroid follicular adenomas between 8-12 months of age compared to 12% of males

increased thyroid carcinoma incidence ( J:165293 )

• 50% of the females and 35% of males over one year of age develop invasive and often metastatic thyroid follicular carcinomas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
follicular thyroid carcinoma		DOID:3962	OMIM:188470	J:165293

Allelic Composition	Gt(ROSA)26Sor^{tm1(CAG-MYCN,-luc)Jhsc}/Gt(ROSA)26Sor⁺ Pten^tm2.1Ppp/Pten^tm2.1Ppp Rb1^tm2Brn/Rb1⁺ Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sor^{tm1(CAG-MYCN,-luc)Jhsc} mutation (0 available); any Gt(ROSA)26Sor mutation (993 available)
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Rb1^tm2Brn mutation (3 available); any Rb1 mutation (111 available)
Tg(Pbsn-cre)4Prb mutation (2 available)

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

mortality/aging

premature death ( J:307910 )

• median survival time of 19 weeks

neoplasm

increased prostate gland tumor incidence ( J:307910 )

• mice develop large, invasive tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 12 weeks

• these regions show little resemblance to conventional adenocarcinoma but are negative for neuroendocrine markers, potentially as a transition between conventional adenocarcinoma and neuroendocrine prostate cancer (NEPC) states

• some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology

• tumors also include other foci of divergent differentiation like intestinal and squamous, as well as conventional, AR+ adenocarcinoma, but the percentage of conventional adenocarcinoma decreases over time while the percentage of poorly differentiated histology increases over time

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:307910 )

• mice develop large, invasive tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 12 weeks

• some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology

reproductive system

increased prostate gland tumor incidence ( J:307910 )

• mice develop large, invasive tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 12 weeks

• some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate neuroendocrine neoplasm		DOID:2992		J:307910

Allelic Composition	Gt(ROSA)26Sor^{tm1(CAG-MYCN,-luc)Jhsc}/Gt(ROSA)26Sor⁺ Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2

Find Mice

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

mortality/aging

premature death ( J:307910 )

• median survival time of 26 weeks

• castrated mice have a median survival time of 44 weeks

neoplasm

increased prostate intraepithelial neoplasia incidence ( J:307910 )

• mice develop prostate tumors that have primarily high-grade prostatic intraepithelial neoplasia at earlier time points

• tumors regress post-castration but resume growth 24 weeks post-castration

endocrine/exocrine glands

increased prostate intraepithelial neoplasia incidence ( J:307910 )

• mice develop prostate tumors that have primarily high-grade prostatic intraepithelial neoplasia at earlier time points

• tumors regress post-castration but resume growth 24 weeks post-castration

reproductive system

increased prostate intraepithelial neoplasia incidence ( J:307910 )

• mice develop prostate tumors that have primarily high-grade prostatic intraepithelial neoplasia at earlier time points

• tumors regress post-castration but resume growth 24 weeks post-castration

Allelic Composition	Pten^tm2.1Ppp/Pten^tm2.1Ppp Rb1^tm2Brn/Rb1^tm2Brn Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Rb1^tm2Brn mutation (3 available); any Rb1 mutation (111 available)
Tg(Pbsn-cre)4Prb mutation (2 available)

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

mortality/aging

premature death ( J:307910 )

• median survival time of 38 weeks

• castrated mice have a median survival time of 43.5 weeks

neoplasm

increased prostate intraepithelial neoplasia incidence ( J:307910 )

• prostates from 8-week-old mice are composed of androgen receptor-positive, high-grade prostatic intraepithelial neoplasia lesions

• tumors regress post-castration but resume growth 24 weeks post-castration

endocrine/exocrine glands

increased prostate intraepithelial neoplasia incidence ( J:307910 )

• prostates from 8-week-old mice are composed of androgen receptor-positive, high-grade prostatic intraepithelial neoplasia lesions

• tumors regress post-castration but resume growth 24 weeks post-castration

reproductive system

increased prostate intraepithelial neoplasia incidence ( J:307910 )

• prostates from 8-week-old mice are composed of androgen receptor-positive, high-grade prostatic intraepithelial neoplasia lesions

• tumors regress post-castration but resume growth 24 weeks post-castration

Allelic Composition	Gt(ROSA)26Sor^{tm1(CAG-MYCN,-luc)Jhsc}/Gt(ROSA)26Sor⁺ Pten^tm2.1Ppp/Pten^tm2.1Ppp Rb1^tm2Brn/Rb1^tm2Brn Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129 * 129S1/Sv * 129S6/SvEvTac * C57BL/6 * DBA/2

Find Mice

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

mortality/aging

premature death ( J:307910 )

• median survival time of 12.5 weeks

• castrated mice have a median survival time of 24 weeks

neoplasm

increased prostate gland tumor incidence ( J:307910 )

• mice develop large, invasive prostate tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 8 weeks

• some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology

• mice do not respond to surgical castration and continue to grow tumors rapidly

• post-castration tumors harbor foci enriched with divergent differentiated histology compared to adenocarcinoma and increased metastatic potential

increased metastatic potential ( J:307910 )

• onset of metastasis occurs as early as 8 weeks and by 12 weeks, 100% of mice develop distant metastatic lesions; metastases to the lung, liver, lymph nodes, and kidney primarily consist of large and small cell neuroendocrine histologies that are AR-negative

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:307910 )

• mice develop large, invasive prostate tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 8 weeks

• some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology

• mice do not respond to surgical castration and continue to grow tumors rapidly

• post-castration tumors harbor foci enriched with divergent differentiated histology compared to adenocarcinoma and increased metastatic potential

reproductive system

increased prostate gland tumor incidence ( J:307910 )

• mice develop large, invasive prostate tumors with androgen receptor (AR)-negative and poorly differentiated foci as early as 8 weeks

• some foci are positive for neuroendocrine markers INSM1, EZH2, and NKX2-1 and some foci display condensed nuclei and scant cytoplasm, characteristic of NEPC morphology

• mice do not respond to surgical castration and continue to grow tumors rapidly

• post-castration tumors harbor foci enriched with divergent differentiated histology compared to adenocarcinoma and increased metastatic potential

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate neuroendocrine neoplasm		DOID:2992		J:307910

Allelic Composition	Pik3cd^tm1Tnr/Pik3cd^tm1Tnr Pten^tm2.1Ppp/Pten^tm2.1Ppp Cd19^tm1(cre)Cgn/Cd19⁺
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * 129S4/SvJae * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cd19^tm1(cre)Cgn mutation (11 available); any Cd19 mutation (60 available)
Pik3cd^tm1Tnr mutation (0 available); any Pik3cd mutation (45 available)
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)

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

immune system

immune system phenotype ( J:130950 )

N	• unlike in Pten deficient mice, B1 B cell numbers are normal in the spleen and peritoneum

abnormal class switch recombination ( J:130950 )

• defects in class switch recombination associated with Pten deficiency are partially reversed

increased marginal zone B cell number ( J:130950 )

• mice exhibit an increase in marginal zone B cells that is not as great as in Pten null mice but more than in wild-type mice

hematopoietic system

abnormal class switch recombination ( J:130950 )

• defects in class switch recombination associated with Pten deficiency are partially reversed

increased marginal zone B cell number ( J:130950 )

• mice exhibit an increase in marginal zone B cells that is not as great as in Pten null mice but more than in wild-type mice

Allelic Composition	Pten^tm2.1Ppp/Pten⁺ Spry1^tm1Jdli/Spry1^tm1.1Jdli Spry2^tm1Mrt/Spry2^tm1.1Mrt Tg(Osr1-cre)4Mrt/0
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Spry1^tm1.1Jdli mutation (0 available); any Spry1 mutation (16 available)
Spry1^tm1Jdli mutation (1 available); any Spry1 mutation (16 available)
Spry2^tm1.1Mrt mutation (1 available); any Spry2 mutation (24 available)
Spry2^tm1Mrt mutation (1 available); any Spry2 mutation (24 available)
Tg(Osr1-cre)4Mrt mutation (1 available)

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

neoplasm

increased prostate gland tumor incidence ( J:192348 )

• evidence of invasion, including clusters of epithelial cells in the mesenchyme and vasculature and loss of the smooth muscle around ducts, is seen associated with high-grade PIN, indicating transition to invasive cancer

increased prostate intraepithelial neoplasia incidence ( J:192348 )

• prostates at 6 months of age show multiple, widely spaced areas with low-grade PIN and occasional ducts with high-grade PIN

• at 12-14 months of age, about 50% of ducts show low-grade PIN and about 15% show high-grade PIN compared to 5-10% of control ducts showing PIN

• ductal lumens are filled with atypical and dysplastic cells that distort the overall ductal architecture and are associated with areas of necrosis and abnormal intraepithelial vessels typical of high-grade PIN

reproductive system

increased prostate gland tumor incidence ( J:192348 )

increased prostate intraepithelial neoplasia incidence ( J:192348 )

• prostates at 6 months of age show multiple, widely spaced areas with low-grade PIN and occasional ducts with high-grade PIN

• at 12-14 months of age, about 50% of ducts show low-grade PIN and about 15% show high-grade PIN compared to 5-10% of control ducts showing PIN

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:192348 )

increased prostate intraepithelial neoplasia incidence ( J:192348 )

• prostates at 6 months of age show multiple, widely spaced areas with low-grade PIN and occasional ducts with high-grade PIN

• at 12-14 months of age, about 50% of ducts show low-grade PIN and about 15% show high-grade PIN compared to 5-10% of control ducts showing PIN

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:192348

Allelic Composition	Braf^tm1Mmcm/Braf⁺ Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Tyr-cre/ERT2)13Bos/0
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * FVB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Braf^tm1Mmcm mutation (3 available); any Braf mutation (60 available)
Pten^tm2.1Ppp 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

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

increased metastatic potential ( J:151023 )

• spread of melanoma in 4-HT treated mice 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	Braf^tm1Mmcm/Braf⁺ Pten^tm2.1Ppp/Pten⁺ Tg(Tyr-cre/ERT2)13Bos/0
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * FVB

Find Mice

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

integument

increased cutaneous melanoma incidence ( J:151023 )

• 4-HT treated mice eventually develop focal malignant melanomas

neoplasm

increased cutaneous melanoma incidence ( J:151023 )

• 4-HT treated mice eventually develop focal malignant melanomas

pigmentation

abnormal melanocyte morphology ( J:151023 )

• 4-hydroxytamoxifen (4-HT) treated mice initially develop benign melanocytic lesions but they eventually develop focal malignant melanomas

Allelic Composition	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(CAG-Bgeo,-Spry2,-ALPP)1Mrt/0 Tg(Osr1-cre)4Mrt/0
Genetic Background	involves: 129P2/OlaHsd * 129S1/Sv * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(CAG-Bgeo,-Spry2,-ALPP)1Mrt mutation (1 available)
Tg(Osr1-cre)4Mrt mutation (1 available)

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

neoplasm

increased prostate intraepithelial neoplasia incidence ( J:192348 )

• PIN is seen in 15% of prostate ducts as early as 2 weeks of age, in 31% of ducts at 4 weeks, and 42% of ducts at 9 months of age

reproductive system

increased prostate intraepithelial neoplasia incidence ( J:192348 )

• PIN is seen in 15% of prostate ducts as early as 2 weeks of age, in 31% of ducts at 4 weeks, and 42% of ducts at 9 months of age

endocrine/exocrine glands

increased prostate intraepithelial neoplasia incidence ( J:192348 )

• PIN is seen in 15% of prostate ducts as early as 2 weeks of age, in 31% of ducts at 4 weeks, and 42% of ducts at 9 months of age

Allelic Composition	Hras^tm1Jaf/Hras^tm1Jaf Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0
Genetic Background	involves: 129S1/Sv * 129S6/SvEvTac * FVB/NCr

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Hras^tm1Jaf mutation (0 available); any Hras mutation (30 available)
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(TPO-cre)1Shk mutation (1 available)

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

endocrine/exocrine glands

increased thyroid tumor incidence ( J:231492 )

• mice develop poorly differentiated thyroid cancer

neoplasm

increased thyroid tumor incidence ( J:231492 )

• mice develop poorly differentiated thyroid cancer

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thyroid cancer		DOID:1781		J:231492

Allelic Composition	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tnfrsf4^tm2(cre)Nik/Tnfrsf4⁺
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tnfrsf4^tm2(cre)Nik mutation (1 available); any Tnfrsf4 mutation (36 available)

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

immune system

increased germinal center B cell number ( J:164283 )

• following immunization

increased T follicular helper cell number ( J:164283 )

• 3-fold following immunization

increased IgG1 level ( J:164283 )

• following immunization, mice exhibit an increased in high-affinity antibody titers compared to in similarly treated wild-type mice

hematopoietic system

increased germinal center B cell number ( J:164283 )

• following immunization

increased T follicular helper cell number ( J:164283 )

• 3-fold following immunization

increased IgG1 level ( J:164283 )

• following immunization, mice exhibit an increased in high-affinity antibody titers compared to in similarly treated wild-type mice

Allelic Composition	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Osr1-cre)4Mrt/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(Osr1-cre)4Mrt mutation (1 available)

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

neoplasm

increased prostate intraepithelial neoplasia incidence ( J:192348 )

• PIN is seen in 31% of prostate ducts as early as 2 weeks of age, in 66% of ducts at 4 weeks, and 79% of ducts at 9 months of age show extensive high-grade PIN

reproductive system

increased prostate intraepithelial neoplasia incidence ( J:192348 )

• PIN is seen in 31% of prostate ducts as early as 2 weeks of age, in 66% of ducts at 4 weeks, and 79% of ducts at 9 months of age show extensive high-grade PIN

endocrine/exocrine glands

increased prostate intraepithelial neoplasia incidence ( J:192348 )

• PIN is seen in 31% of prostate ducts as early as 2 weeks of age, in 66% of ducts at 4 weeks, and 79% of ducts at 9 months of age show extensive high-grade PIN

Allelic Composition	Eif4e^tm1.1Lfur/Eif4e^tm1.1Lfur Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Eif4e^tm1.1Lfur mutation (0 available); any Eif4e mutation (42 available)
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(Pbsn-cre)4Prb mutation (2 available)

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

neoplasm

decreased tumor incidence ( J:163589 )

• at 7 months, mice exhibit fewer incidence of high grade prostate intraepithelial neoplasia due to delayed onset and decreased cell proliferation compared with Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb mice

• mice do not exhibit infiltrating adenocarcinoma in the prostate unlike Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb mice

Allelic Composition	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)8113ANg/0
Genetic Background	involves: 129S1/Sv * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(Pbsn-cre)8113ANg mutation (0 available)

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

neoplasm

increased prostate gland tumor incidence ( J:86212 )

• complete penetrance of invasive and diffuse prostate cancer

• disruption of basement membrane and organ infiltration

• tumors were less diffuse than in homozygotes carrying Tg(Pbsn-cre)4Prb, variably differentiated, and only affected a single lobe

endocrine/exocrine glands

abnormal prostate gland morphology ( J:86212 )

• irregular cells

prostate gland epithelial hyperplasia ( J:86212 )

• focal areas of epithelial hyperplasia

• increased proliferation of epithelial cells

enlarged prostate gland ( J:86212 )

• enlargement of prostate, less pronounced than in homozygotes carrying Tg(Pbsn-cre)4Prb

increased prostate gland tumor incidence ( J:86212 )

• complete penetrance of invasive and diffuse prostate cancer

• disruption of basement membrane and organ infiltration

• tumors were less diffuse than in homozygotes carrying Tg(Pbsn-cre)4Prb, variably differentiated, and only affected a single lobe

reproductive system

abnormal prostate gland morphology ( J:86212 )

• irregular cells

prostate gland epithelial hyperplasia ( J:86212 )

• focal areas of epithelial hyperplasia

• increased proliferation of epithelial cells

enlarged prostate gland ( J:86212 )

• enlargement of prostate, less pronounced than in homozygotes carrying Tg(Pbsn-cre)4Prb

increased prostate gland tumor incidence ( J:86212 )

• complete penetrance of invasive and diffuse prostate cancer

• disruption of basement membrane and organ infiltration

• tumors were less diffuse than in homozygotes carrying Tg(Pbsn-cre)4Prb, variably differentiated, and only affected a single lobe

Allelic Composition	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(GFAP-TAg121)1Tvd/0
Genetic Background	involves: 129S1/Sv * C57BL/6 * C57BL/6J * DBA/2 * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(GFAP-TAg121)1Tvd mutation (0 available)

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

nervous system

abnormal brain vasculature morphology ( J:99385 )

• mice infected with a cre-expression virus exhibit increased angiogenesis in the cerebral cortex compared to in control mice

abnormal astrocyte apoptosis ( J:99385 )

• mice infected with a cre-expression virus exhibit astrocytmoa with increased invasiveness compared with mice expressing Tg(GFAP-TAg121)1Tvd

increased astrocytoma incidence ( J:99385 )

• mice infected with a cre-expression virus exhibit astrocytmoa with increased invasiveness compared with mice expressing Tg(GFAP-TAg121)1Tvd

neoplasm

increased astrocytoma incidence ( J:99385 )

• mice infected with a cre-expression virus exhibit astrocytmoa with increased invasiveness compared with mice expressing Tg(GFAP-TAg121)1Tvd

cardiovascular system

abnormal brain vasculature morphology ( J:99385 )

• mice infected with a cre-expression virus exhibit increased angiogenesis in the cerebral cortex compared to in control mice

increased angiogenesis ( J:99385 )

• in cerebral cortex injected with cre-expressing virus

cellular

abnormal astrocyte apoptosis ( J:99385 )

• mice infected with a cre-expression virus exhibit astrocytmoa with increased invasiveness compared with mice expressing Tg(GFAP-TAg121)1Tvd

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant astrocytoma		DOID:3069		J:99385

Allelic Composition	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129S1/Sv * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(Pbsn-cre)4Prb mutation (2 available)

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

reproductive system

abnormal prostate gland morphology ( J:86212 )

• large, irregular cells, occasionally forming cryptic glandular structures

abnormal prostate gland epithelium morphology ( J:86212 )

• prostate epithelial dysplasia

prostate gland epithelial hyperplasia ( J:86212 , J:100683 )

• focal areas of epithelial hyperplasia (J:86212)

• increased proliferation of epithelial cells (J:86212)

• mutant prostates contain a 20-fold increase in senescent epithelial cells compared to wild-type prostates (J:100683)

enlarged prostate gland ( J:86212 )

• massive enlargement of all prostatic lobes evident at 2 to 3 months of age, complete penetrance

prostate gland hyperplasia ( J:86212 )

increased prostate gland tumor incidence ( J:86212 , J:100683 )

• tumors were undifferentiated and often affected multiple lobes, suggesting multifocal origns (J:86212)

• complete penetrance of invasive and diffuse prostate cancer with disruption of basement membrane and signs of organ infiltration (J:86212)

• invasive prostatic cancer develops after a 4-6 month latency; however none of the mutants had died of prostatic cancer by 10 months of age (J:100683)

• tumors retain clearly defined urogenital organ boundaries (J:100683)

increased prostate gland adenocarcinoma incidence ( J:100683 , J:163589 )

(J:100683)

(J:163589)

increased prostate intraepithelial neoplasia incidence ( J:100683 , J:163589 , J:200002 , J:239660 )

• high-grade prostatic intraepithelial neoplasia are seen in all 3 prostatic lobes in 9-week old mutants (J:100683)

(J:163589)

• that does not progress to grossly invasive disease (J:200002)

• mice develop diffuse, highly proliferative high-grade prostatic intraepithelial neoplasia without invasive cancer but with cystic enlargement of the anterior prostate (J:239660)

neoplasm

increased prostate gland tumor incidence ( J:86212 , J:100683 )

• tumors were undifferentiated and often affected multiple lobes, suggesting multifocal origns (J:86212)

• complete penetrance of invasive and diffuse prostate cancer with disruption of basement membrane and signs of organ infiltration (J:86212)

• invasive prostatic cancer develops after a 4-6 month latency; however none of the mutants had died of prostatic cancer by 10 months of age (J:100683)

• tumors retain clearly defined urogenital organ boundaries (J:100683)

increased prostate gland adenocarcinoma incidence ( J:100683 , J:163589 )

(J:100683)

(J:163589)

increased prostate intraepithelial neoplasia incidence ( J:100683 , J:163589 , J:200002 , J:239660 )

• high-grade prostatic intraepithelial neoplasia are seen in all 3 prostatic lobes in 9-week old mutants (J:100683)

(J:163589)

• that does not progress to grossly invasive disease (J:200002)

• mice develop diffuse, highly proliferative high-grade prostatic intraepithelial neoplasia without invasive cancer but with cystic enlargement of the anterior prostate (J:239660)

endocrine/exocrine glands

abnormal prostate gland morphology ( J:86212 )

• large, irregular cells, occasionally forming cryptic glandular structures

abnormal prostate gland epithelium morphology ( J:86212 )

• prostate epithelial dysplasia

prostate gland epithelial hyperplasia ( J:86212 , J:100683 )

• focal areas of epithelial hyperplasia (J:86212)

• increased proliferation of epithelial cells (J:86212)

• mutant prostates contain a 20-fold increase in senescent epithelial cells compared to wild-type prostates (J:100683)

enlarged prostate gland ( J:86212 )

• massive enlargement of all prostatic lobes evident at 2 to 3 months of age, complete penetrance

prostate gland hyperplasia ( J:86212 )

increased prostate gland tumor incidence ( J:86212 , J:100683 )

• tumors were undifferentiated and often affected multiple lobes, suggesting multifocal origns (J:86212)

• complete penetrance of invasive and diffuse prostate cancer with disruption of basement membrane and signs of organ infiltration (J:86212)

• invasive prostatic cancer develops after a 4-6 month latency; however none of the mutants had died of prostatic cancer by 10 months of age (J:100683)

• tumors retain clearly defined urogenital organ boundaries (J:100683)

increased prostate gland adenocarcinoma incidence ( J:100683 , J:163589 )

(J:100683)

(J:163589)

increased prostate intraepithelial neoplasia incidence ( J:100683 , J:163589 , J:200002 , J:239660 )

• high-grade prostatic intraepithelial neoplasia are seen in all 3 prostatic lobes in 9-week old mutants (J:100683)

(J:163589)

• that does not progress to grossly invasive disease (J:200002)

• mice develop diffuse, highly proliferative high-grade prostatic intraepithelial neoplasia without invasive cancer but with cystic enlargement of the anterior prostate (J:239660)

Allelic Composition	Pten^tm2.1Ppp/Pten^tm2.1Ppp Trp53^tm1Thl/Trp53^tm1Thl Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129S1/Sv * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(Pbsn-cre)4Prb mutation (2 available)
Trp53^tm1Thl mutation (0 available); any Trp53 mutation (240 available)

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

mortality/aging

premature death ( J:100683 )

• all mutants died by 7 months of age

neoplasm

increased prostate gland tumor incidence ( J:100683 )

• invasive prostatic cancer is seen in all mutants by 10 weeks of age

• average tumor weight is increased 32-fold compared to mutants wild-type for Trp53 and these tumors encompass the entire genitourinary tract and pelvis

• no increase is seen in the number of senescent cells compared to wild-type prostates unlike in mutants wild-type for Trp53

increased carcinoma incidence ( J:100683 )

• by 11 weeks of age invasive adenocarcinoma develops

renal/urinary system

urinary bladder obstruction ( J:100683 )

• bladder obstruction

kidney failure ( J:100683 )

reproductive system

increased prostate gland tumor incidence ( J:100683 )

• invasive prostatic cancer is seen in all mutants by 10 weeks of age

• average tumor weight is increased 32-fold compared to mutants wild-type for Trp53 and these tumors encompass the entire genitourinary tract and pelvis

• no increase is seen in the number of senescent cells compared to wild-type prostates unlike in mutants wild-type for Trp53

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:100683 )

• invasive prostatic cancer is seen in all mutants by 10 weeks of age

• average tumor weight is increased 32-fold compared to mutants wild-type for Trp53 and these tumors encompass the entire genitourinary tract and pelvis

• no increase is seen in the number of senescent cells compared to wild-type prostates unlike in mutants wild-type for Trp53

Allelic Composition	Gt(ROSA)26Sor^{tm1(TMPRSS2/ERG)Key}/Gt(ROSA)26Sor^{tm1(TMPRSS2/ERG)Key} Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129S1/Sv * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sor^{tm1(TMPRSS2/ERG)Key} mutation (2 available); any Gt(ROSA)26Sor mutation (993 available)
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(Pbsn-cre)4Prb mutation (2 available)

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

mortality/aging

premature death ( J:200002 )

• shortened survival compared with Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb mice

reproductive system

enlarged prostate gland ( J:200002 )

• enlarged and hardened by 6 months

increased prostate gland adenocarcinoma incidence ( J:200002 )

• invasive with small irregular glandular structures composed of malignant cells with large, pleiomorphic nuclei and pale cytoplasm by 8 weeks

increased prostate intraepithelial neoplasia incidence ( J:200002 )

• with a proliferative index only slightly higher than in Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb mice

abnormal prostate gland physiology ( J:200002 )

• proliferative index only slightly higher than in Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb mice

penis prolapse ( J:200002 )

neoplasm

increased prostate gland adenocarcinoma incidence ( J:200002 )

• invasive with small irregular glandular structures composed of malignant cells with large, pleiomorphic nuclei and pale cytoplasm by 8 weeks

increased prostate intraepithelial neoplasia incidence ( J:200002 )

• with a proliferative index only slightly higher than in Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb mice

renal/urinary system

penis prolapse ( J:200002 )

growth/size/body

distended abdomen ( J:200002 )

• increased abdominal girth

endocrine/exocrine glands

enlarged prostate gland ( J:200002 )

• enlarged and hardened by 6 months

increased prostate gland adenocarcinoma incidence ( J:200002 )

• invasive with small irregular glandular structures composed of malignant cells with large, pleiomorphic nuclei and pale cytoplasm by 8 weeks

increased prostate intraepithelial neoplasia incidence ( J:200002 )

• with a proliferative index only slightly higher than in Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb mice

abnormal prostate gland physiology ( J:200002 )

• proliferative index only slightly higher than in Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb mice

Allelic Composition	Gt(ROSA)26Sor^{tm1(SPOP*F133V)Mrbn}/Gt(ROSA)26Sor⁺ Pten^tm2.1Ppp/Pten⁺ Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129S1/Sv * C57BL/6 * DBA/2

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sor^{tm1(SPOP*F133V)Mrbn} mutation (1 available); any Gt(ROSA)26Sor mutation (993 available)
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(Pbsn-cre)4Prb mutation (2 available)

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

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:239660 )

• 1 of 5 mice older than 12 months exhibit areas of invasive prostate carcinoma

increased prostate intraepithelial neoplasia incidence ( J:239660 )

• mice exhibit a high penetrance of focal areas of high-grade prostatic intraepithelial neoplasia by 6 months of age, characterized by nuclear atypia

neoplasm

increased prostate gland adenocarcinoma incidence ( J:239660 )

• 1 of 5 mice older than 12 months exhibit areas of invasive prostate carcinoma

increased prostate intraepithelial neoplasia incidence ( J:239660 )

• mice exhibit a high penetrance of focal areas of high-grade prostatic intraepithelial neoplasia by 6 months of age, characterized by nuclear atypia

reproductive system

increased prostate gland adenocarcinoma incidence ( J:239660 )

• 1 of 5 mice older than 12 months exhibit areas of invasive prostate carcinoma

increased prostate intraepithelial neoplasia incidence ( J:239660 )

• mice exhibit a high penetrance of focal areas of high-grade prostatic intraepithelial neoplasia by 6 months of age, characterized by nuclear atypia

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:239660

Allelic Composition	Gt(ROSA)26Sor^{tm1(SPOP*F133V)Mrbn}/Gt(ROSA)26Sor⁺ Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Pbsn-cre)4Prb/0
Genetic Background	involves: 129S1/Sv * C57BL/6 * DBA/2

Find Mice

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

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:239660 )

• mice exhibit severely enlarged prostates with areas of solid tumor by 12 months of age

• 80% of mice display invasive, poorly differentiated carcinomas; tumors are highly proliferative with transitional sarcomatoid differentiation and maintain expression of androgen receptor

neoplasm

increased prostate gland adenocarcinoma incidence ( J:239660 )

• mice exhibit severely enlarged prostates with areas of solid tumor by 12 months of age

• 80% of mice display invasive, poorly differentiated carcinomas; tumors are highly proliferative with transitional sarcomatoid differentiation and maintain expression of androgen receptor

reproductive system

increased prostate gland adenocarcinoma incidence ( J:239660 )

• mice exhibit severely enlarged prostates with areas of solid tumor by 12 months of age

• 80% of mice display invasive, poorly differentiated carcinomas; tumors are highly proliferative with transitional sarcomatoid differentiation and maintain expression of androgen receptor

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:239660

Allelic Composition	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Dhh-cre)1Mejr/0
Genetic Background	involves: 129S1/Sv * C57BL/6 * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(Dhh-cre)1Mejr mutation (1 available)

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

mortality/aging

premature death ( J:195067 )

• median survival age is 247 days compared to conditional Pten heterozygotes that have a median survival age of 415 days

nervous system

abnormal nervous system morphology ( J:195067 )

• mutants exhibit a similar peripheral nervous system phenotype as triple homozygous Pten^tm2.1Ppp Tg(Dhh-cre)1Mejr/0 Tg(Cnp-EGFR)10Nrat/0 mutants but with delayed latency and reduced tumor multiplicity

• 100% exhibit enlarged branchial plexi

• 10% exhibit enlarged sacral plexi

increased neurofibrosarcoma incidence ( J:195067 )

• enlarged peripheral nerves are low-grade peripheral nerve sheath tumors (PNSTs)

abnormal trigeminal nerve morphology ( J:195067 )

• 90% exhibit enlarged trigeminal nerves

abnormal sciatic nerve morphology ( J:195067 )

• 80% exhibit enlarged sciatic nerves

neoplasm

increased neurofibrosarcoma incidence ( J:195067 )

• enlarged peripheral nerves are low-grade peripheral nerve sheath tumors (PNSTs)

Allelic Composition	Pten^tm2.1Ppp/Pten⁺ Tg(Cnp-EGFR)10Nrat/0 Tg(Dhh-cre)1Mejr/0
Genetic Background	involves: 129S1/Sv * C57BL/6 * FVB/N * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp mutation (0 available); any Pten mutation (88 available)
Tg(Cnp-EGFR)10Nrat mutation (0 available)
Tg(Dhh-cre)1Mejr mutation (1 available)

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

nervous system

abnormal nervous system morphology ( J:195067 )

• mice display a similar peripheral nervous system phenotype as homozygous Pten^tm2.1Ppp Tg(Dhh-cre)1Mejr/0 mice, except with a latency of 415 days

• 100% exhibit enlarged branchial plexi

• 20% exhibit enlarged sacral plexi

increased neurofibrosarcoma incidence ( J:195067 )

• enlarged peripheral nerves are graded as hyperplasia to low-grade grade peripheral nerve sheath tumors (PNSTs)

abnormal trigeminal nerve morphology ( J:195067 )

• 100% exhibit enlarged trigeminal nerves

abnormal sciatic nerve morphology ( J:195067 )

• 80% exhibit enlarged sciatic nerves

neoplasm

increased neurofibrosarcoma incidence ( J:195067 )

• enlarged peripheral nerves are graded as hyperplasia to low-grade grade peripheral nerve sheath tumors (PNSTs)

Allelic Composition	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Cnp-EGFR)10Nrat/0 Tg(Dhh-cre)1Mejr/0
Genetic Background	involves: 129S1/Sv * C57BL/6 * FVB/N * SJL

Find Mice

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

mortality/aging

premature death ( J:195067 )

• rapid postnatal death, with a medial survival age of 26 days

nervous system

abnormal nervous system morphology ( J:195067 )

• mutants exhibit enlarged peripheral nerves: brachial plexi, sacral plexi, trigeminal and sciatic nerves

• 100% exhibit enlarged branchial plexi

• 50% exhibit enlarged lumbar sacral plexi

• mast cells are seen in enlarged peripheral nerves

increased neurofibrosarcoma incidence ( J:195067 )

• enlarged peripheral nerves are graded as high-grade grade peripheral nerve sheath tumors (PNSTs) resembling human sporatic malignant grade peripheral nerve sheath tumors

abnormal trigeminal nerve morphology ( J:195067 )

• 92% exhibit enlarged trigeminal nerves

enlarged dorsal root ganglion ( J:195067 )

• mutants exhibit multiple enlarged dorsal root ganglia

abnormal sciatic nerve morphology ( J:195067 )

• 50% exhibit enlarged sciatic nerves

neoplasm

increased neurofibrosarcoma incidence ( J:195067 )

• enlarged peripheral nerves are graded as high-grade grade peripheral nerve sheath tumors (PNSTs) resembling human sporatic malignant grade peripheral nerve sheath tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant peripheral nerve sheath tumor		DOID:5940		J:195067

Allelic Composition	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Tyr-cre/ERT2)13Bos/0
Genetic Background	involves: 129S1/Sv * FVB

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pten^tm2.1Ppp 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

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