Phenotypes associated with this allele

• Allele Symbol: Pten⁺
• Allele Name: wild type
• Allele ID: MGI:2179023
• Summary: 65 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Pten^tm1Mak/Pten^+	B6.129P2-Pten^tm1Mak	MGI:3717269
ht2	Pten^tm1Rps/Pten^+	B6.129S1-Pten^tm1Rps	MGI:5467726
ht3	Pten^tm1Rps/Pten^+	B6.129S1-Pten^tm1Rps/Nci	MGI:5805821
ht4	Pten^tm1Engc/Pten^+	either: (involves: 129 * CD-1) or (involves: 129 * A/J * C57BL/6J) or (involves: 129 * C57BL/6J * CD-1)	MGI:5509202
ht5	Pten^tm1Mak/Pten^+	involves: 129P2/OlaHsd * C57BL/6J	MGI:2179030
ht6	Pten^tm1Rps/Pten^+	involves: 129S1/Sv * 129S1/SvImJ * C57BL/6J	MGI:5569932
ht7	Pten^tm1Rps/Pten^+	involves: 129S1/Sv * C57BL/6J	MGI:2179045
ht8	Pten^tm1Ppp/Pten^+	involves: 129S1/Sv * C57BL/6J	MGI:2179025
ht9	Pten^tm1Hwu/Pten^+	involves: 129S4/SvJae * BALB/c	MGI:3707147
ht10	Pten^tm2Hwu/Pten^+	involves: 129S4/SvJae * BALB/c	MGI:3707124
ht11	Pten^tm1.1Hwu/Pten^+	involves: 129S4/SvJae * BALB/c	MGI:3707122
ht12	Pten^tm1.1Hwu/Pten^+	involves: 129S4/SvJae * BALB/c * C57BL/6	MGI:3707123
ht13	Pten^tm2Hwu/Pten^+	involves: 129S4/SvJae * C57BL/6	MGI:3707125
ht14	Pten^tm1.1Hwu/Pten^+	involves: 129S4/SvJae * C57BL/6NTac	MGI:5008590
ht15	Pten^tm1.2Mwst/Pten^+	involves: 129S6/SvEvTac * Black Swiss * FVB/N	MGI:6512404
ht16	Pten^tm1.1Gle/Pten^+	involves: 129S6/SvEvTac * Black Swiss * FVB/N	MGI:4442333
ht17	Pten^tm2.1Gle/Pten^+	involves: 129S6/SvEvTac * Black Swiss * FVB/N	MGI:4442335
ht18	Pten^tm1Engc/Pten^+	involves: CD-1	MGI:5509200
ht19	Pten^tm1.1Mro/Pten^+	Not Specified	MGI:5812675
cn20	Pten^tm1Hwu/Pten^+ Tg(Nkx2-1-cre)2Sand/0	B6.Cg-Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand	MGI:5517709
cn21	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
cn22	Braf^tm1Mmcm/Braf^+ Pten^tm2.1Ppp/Pten^+ Tg(Tyr-cre/ERT2)13Bos/0	involves: 129P2/OlaHsd * 129S1/Sv * FVB	MGI:5902136
cn23	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
cn24	Kras^tm4Tyj/Kras^+ Pten^tm2Mak/Pten^+ Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA	MGI:6256732
cn25	Pten^tm1Rdp/Pten^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(GFAP-cre)25Mes/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:3831280
cn26	Gt(ROSA)26Sor^tm1(CAG-Bmi1,-EGFP)Nki/Gt(ROSA)26Sor^+ Pten^tm1Mro/Pten^+ Tg(Pbsn-cre)4Prb/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2 * FVB/N	MGI:5427498
cn27	Pten^tm1Mro/Pten^+ Tg(KLK3-cre)D4Trp/0	involves: 129P2/OlaHsd * FVB	MGI:3761927
cn28	Nf1^tm1Par/Nf1^+ Pten^tm1Hwu/Pten^+ Trp53^tm1Tyj/Trp53^+ Tg(GFAP-cre)25Mes/0	involves: 129S1/Sv * 129S2/SvPas * 129S4/SvJae * 129X1/SvJ * FVB/N	MGI:4840094
cn29	Nf1^tm1Par/Nf1^+ Pten^tm1Hwu/Pten^+ Tg(Gfap-cre)77.6Mvs/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6NHsd	MGI:4849443
cn30	Erbb2^tm8(Erbb2)Mul/Erbb2^+ Pten^tm1Hwu/Pten^+ Tg(MMTV-cre)7Mul/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N	MGI:4839508
cn31	Nf1^tm1Par/Nf1^+ Pten^tm1Hwu/Pten^+ Trp53^tm1Elee/Trp53^+ Tg(GFAP-cre)25Mes/0	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N	MGI:4840096
cn32	Bcl2l11^tm1.1Ast/Bcl2l11^+ Pten^tm1Hwu/Pten^+ Tg(CD2-icre)4Kio/0	involves: 129S1/Sv * 129S4/SvJae * C57BL/10 * CBA/Ca	MGI:3783573
cn33	Prkar1a^tm1.2Lsk/Prkar1a^+ Pten^tm1.1Mwst/Pten^+ Tg(TPO-cre)1Shk/0	involves: 129S1/Sv * 129X1/SvJ * FVB/NCr	MGI:5897775
cn34	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
cn35	Pten^tm2.1Ppp/Pten^+ Tg(Cnp-EGFR)10Nrat/0 Tg(Dhh-cre)1Mejr/0	involves: 129S1/Sv * C57BL/6 * FVB/N * SJL	MGI:5485415
cn36	Pten^tm1Mro/Pten^+ Sdhb^tm1.1Ics/Sdhb^+ Tg(KLK3-cre)D4Trp/0	involves: 129S2/SvPas * FVB	MGI:5812679
cn37	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^+ Tg(Pdx1-cre)89.1Dam/0	involves: 129S4/SvJae * BALB/c * C57BL/6	MGI:5013916
cn38	Pten^tm1Hwu/Pten^+ Tg(Nkx2-1-cre)2Sand/0	involves: 129S4/SvJae * BALB/c * C57BL/6	MGI:5517675
cn39	Pten^tm1Hwu/Pten^+ Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2	MGI:4420975
cn40	Pten^tm1Hwu/Pten^+ Tg(ARR2/Pbsn-FGF8)3Prb/0 Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2	MGI:4843916
cn41	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^+ Tg(Gfap-cre)77.6Mvs/0	involves: 129S4/SvJae * BALB/c * C57BL/6NHsd	MGI:4849441
cn42	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^+ Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:5705328
cn43	Pten^tm1Hwu/Pten^+ Tmprss2^tm2.1(ETV1)Sho/Tmprss2^tm2.1(ETV1)Sho Tg(Pbsn-cre)4Prb/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:5578649
cn44	Pten^tm1Hwu/Pten^+ Tg(KRT14-cre)#Smr/0	involves: 129S4/SvJae * C57BL/6J * SJL/J	MGI:3813526
cn45	Kras^tm4Tyj/Kras^+ Pten^tm1Hwu/Pten^+ Tg(Upk2-cre)6Xrw/0	involves: 129S4/SvJae * FVB/N	MGI:5141742
cn46	Pten^tm1Ppp/Pten^+ Rac1^tm1Tyb/Rac1^tm2Tyb Edil3^Tg(Sox2-cre)1Amc/Edil3^+	involves: 129S/Sv * C3H * C57BL/6 * CBA	MGI:5050118
cn47	Pten^tm1Mro/Pten^+ Tg(Pbsn-cre)4Prb/0	involves: C57BL/6 * DBA/2	MGI:5427499
cx48	Pten^tm1Rps/Pten^+ Slc6a4^tm1Kpl/Slc6a4^+	B6.129-Slc6a4^tm1Kpl Pten^tm1Rps	MGI:5467729
cx49	Grhl3^tm1Jane/Grhl3^+ Pten^tm1Mak/Pten^+	involves: 129P2/OlaHsd * 129S1/Sv	MGI:5306661
cx50	Grb2^tm1Paw/Grb2^+ Pten^tm1Mak/Pten^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3717274
cx51	Pten^tm1Rps/Pten^+ Rictor^Gt(RRR347)Byg/Rictor^+	involves: 129P2/OlaHsd * 129S1/Sv * BALB/c * C57BL/6	MGI:4848133
cx52	Nkx3-1^tm1Mms/Nkx3-1^+ Pten^tm1Rps/Pten^+	involves: 129S1/Sv * 129S1/SvImJ * C57BL/6J	MGI:5569928
cx53	Nkx3-1^tm1Mms/Nkx3-1^tm1Mms Pten^tm1Rps/Pten^+	involves: 129S1/Sv * 129S1/SvImJ * C57BL/6J	MGI:5569926
cx54	Mlst8^tm1Lex/Mlst8^+ Pten^tm1Rps/Pten^+	involves: 129S1/Sv * 129S5/SvEvBrd * C57BL/6	MGI:4848146
cx55	Mtor^Gt(OST92090)Lex/Mtor^+ Pten^tm1Rps/Pten^+	involves: 129S1/Sv * 129S5/SvEvBrd * C57BL/6	MGI:4848141
cx56	Akt1^tm1Nhy/Akt1^+ Akt2^tm1Rsg/Akt2^tm1Rsg Pten^tm1Ppp/Pten^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/1LacJ	MGI:3848161
cx57	Akt2^tm1Rsg/Akt2^tm1Rsg Pten^tm1Ppp/Pten^+	involves: 129S1/Sv * C57BL/6 * DBA/1LacJ	MGI:3848162
cx58	Pten^tm1Ppp/Pten^+ Tg(Pbsn-TAg)15Tvd/0	involves: 129S1/Sv * C57BL/6 * DBA/2	MGI:4836243
cx59	Pten^tm1Rps/Pten^+ Tg(Wnt1)1Hev/0	involves: 129S1/Sv * C57BL/6 * FVB/N * SJL	MGI:5442747
cx60	Pten^tm1.1Mro/Pten^+ Sdhb^tm1.2Ics/Sdhb^+	involves: 129S2/SvPas * BALB/c * C57BL/6	MGI:5812674
cx61	Del(16Tmprss2-Erg)1Sho/Del(16Tmprss2-Erg)1Sho Pten^tm1.1Hwu/Pten^+	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:5578651
cx62	Pten^tm1.1Hwu/Pten^+ Tmprss2^tm2.1(ETV1)Sho/Tmprss2^tm2.1(ETV1)Sho	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:5578648
cx63	Pten^tm1.1Hwu/Pten^+ Tmprss2^tm1.1(ERG)Sho/Tmprss2^tm1.1(ERG)Sho	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:5578646
cx64	Gt(ROSA)26Sor^tm1(H1/tetO-RNAi:Pdpk1)Mrl/Gt(ROSA)26Sor^+ Pten^tm1.1Hwu/Pten^+	involves: 129S4/SvJae * C57BL/6NTac	MGI:5008591
cx65	Pten^tm1Rps/Pten^+ Rptor^tm1Lex/Rptor^+	involves: 129S/SvEvBrd * 129S1/Sv * C57BL/6	MGI:4848144

Genotype
MGI:3717269

ht1

• Allelic Composition: Pten^tm1Mak/Pten⁺
• Genetic Background: B6.129P2-Pten^tm1Mak

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

Embryonic defects in Pten^tm1Mak/Pten⁺

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:93530 )

• more than 30% die by E10.5

growth/size/body

decreased embryo size ( J:93530 )

• the majority of embryos are smaller but have normal body symmetry and development of most organ systems

embryo

failure of initiation of embryo turning ( J:93530 )

• majority of embryos remain unturned

abnormal embryonic tissue morphology ( J:93530 )

• severely affected (about 5%) embryos have little or no development of the major organ systems, including the heart and brachial arches

• severely affected (about 5%) embryos have asymmetrical head folds

open neural tube ( J:93530 )

• neural tube is open along the entire length of the embryo

kinked neural tube ( J:93530 )

• neural tube is kinked along the entire length of the embyo

decreased embryo size ( J:93530 )

• the majority of embryos are smaller but have normal body symmetry and development of most organ systems

enlarged allantois ( J:93530 )

abnormal placenta morphology ( J:93530 )

• the remaining 20% of moribound embryos display other placental abnormalities including disorganization of the spongiotrophoblast layer and limited invasion of the trophoblast layer by the chorion

failure of chorioallantoic fusion ( J:93530 )

• the allantois fails to fuse to the chorion at E9 in 80% of dying embryos

nervous system

open neural tube ( J:93530 )

• neural tube is open along the entire length of the embryo

kinked neural tube ( J:93530 )

• neural tube is kinked along the entire length of the embyo

neoplasm

increased tumor incidence ( J:93530 )

increased adrenal gland tumor incidence ( J:93530 )

increased lymphoma incidence ( J:93530 )

increased endometrial carcinoma incidence ( J:93530 )

♀

endocrine/exocrine glands

increased adrenal gland tumor incidence ( J:93530 )

reproductive system

increased endometrial carcinoma incidence ( J:93530 )

♀

Genotype
MGI:5467726

ht2

• Allelic Composition: Pten^tm1Rps/Pten⁺
• Genetic Background: B6.129S1-Pten^tm1Rps

behavior/neurological

abnormal social investigation ( J:144937 )

• 12 week old females do not show preference for spending more time in the social chamber versus nonsocial chamber as wild-type mice do and spend equal time in both chambers, indicating impaired social approach behavior in females but not males

• while 8 week old males do not show a change in preference for social interaction for the first trial, upon reexposure to the same social target in trial 2, males do not show attenuation of preference for social investigation between the first and second trials as seen in wild-type mice

nervous system

increased brain weight ( J:144937 )

decreased prepulse inhibition ( J:144937 )

• both males and females show deficits in prepulse inhibition of the acoustic startle response

• however, mice respond to the olfactory-habituation-dishabituation test normally, indicating normal olfactory function

growth/size/body

megacephaly ( J:144937 )

• macrocephaly in both males and females

Genotype
MGI:5805821

ht3

• Allelic Composition: Pten^tm1Rps/Pten⁺
• Genetic Background: B6.129S1-Pten^tm1Rps/Nci

behavior/neurological

abnormal behavior ( J:235927 )

♂ • males switch between behaviors less often than wild-type mice but spend the same amount of time performing active behaviors

decreased aggression towards male mice ( J:235927 )

♂ • males are involved in less attacking, both delivered to and received from the intruder male which is reflected in decreased agonistic behavior indicating reduced aggression

increased stereotypic behavior ( J:235927 )

♂ • males preform more digging than wild-type mice

abnormal social investigation ( J:235927 )

♂ • males show less social investigation, particularly of the anogenital region and approach and/or attend to the intruder less than wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:235927

Genotype
MGI:5509202

ht4

• Allelic Composition: Pten^tm1Engc/Pten⁺
• Genetic Background: either: (involves: 129 * CD-1) or (involves: 129 * A/J * C57BL/6J) or (involves: 129 * C57BL/6J * CD-1)

nervous system

increased brain weight ( J:200739 )

• after 3 months

growth/size/body

megacephaly ( J:200739 )

Genotype
MGI:2179030

ht5

• Allelic Composition: Pten^tm1Mak/Pten⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

neoplasm

increased tumor incidence ( J:50437 )

• 14% develop spontaneous tumors during a 28 week observation period

increased adrenal gland tumor incidence ( J:63478 )

• 23% show marked expansion and proliferation of chromaffin cells of the adrenal medualla, consistent with medullary hyperplasia or pheochromocytoma; develop after 35 weeks of age

increased mammary gland tumor incidence ( J:63478 )

• 4% of mutants aged 26-29 weeks, 61% aged 30-49 weeks and 83% aged 50-65 weeks develop breast tumors, indicating an increased incidence of breast cancer as mice age

increased fibroadenoma incidence ( J:63478 )

• small breast tumors are classified as fibroadenoma

increased mammary adenocarcinoma incidence ( J:63478 )

• 49% of females develop breast tumors, most classified as Dunn's adenocarcinoma type C

increased prostate gland tumor incidence ( J:63478 )

♂

increased incidence of tumors by ionizing radiation induction ( J:50437 )

• 19% of gamma-irradiated mutants develop tumors compared to none of wild-type

• tumors are thymic lymphomas/leukemias

increased hamartoma incidence ( J:63478 )

• 9% show hamartomatous lesions involving the mucosa of the stomach, duodenum, small bowel, colon, or anorectal junction

increased leukemia incidence ( J:50437 )

• 88% of the tumors are lymphoma/leukemia of the T-cell type

increased lymphoma incidence ( J:63478 )

• older mice develop a range of lymphomas

• 18% develop malignant lymphomas

increased T cell derived lymphoma incidence ( J:50437 )

• 88% of the tumors are lymphoma/leukemia of the T-cell type

increased carcinoma incidence ( J:50437 )

• 33% of tumors are teratocarcinoma

increased endometrial carcinoma incidence ( J:63478 )

♀ • 22% of females develop endometrial carcinoma, with the earliest case found at 30 weeks of age

digestive/alimentary system

enlarged Peyer's patches ( J:63478 )

• enlarged Peyer's patches composed of lymphohistiocytic infiltrates

colon polyps ( J:50437 )

• most mice exhibit microscopic hamartomatous polyps mainly in the colon

endocrine/exocrine glands

increased adrenal gland tumor incidence ( J:63478 )

• 23% show marked expansion and proliferation of chromaffin cells of the adrenal medualla, consistent with medullary hyperplasia or pheochromocytoma; develop after 35 weeks of age

increased T cell derived lymphoma incidence ( J:50437 )

• 88% of the tumors are lymphoma/leukemia of the T-cell type

increased mammary gland tumor incidence ( J:63478 )

• 4% of mutants aged 26-29 weeks, 61% aged 30-49 weeks and 83% aged 50-65 weeks develop breast tumors, indicating an increased incidence of breast cancer as mice age

increased fibroadenoma incidence ( J:63478 )

• small breast tumors are classified as fibroadenoma

increased mammary adenocarcinoma incidence ( J:63478 )

• 49% of females develop breast tumors, most classified as Dunn's adenocarcinoma type C

increased prostate gland tumor incidence ( J:63478 )

♂

abnormal seminiferous tubule morphology ( J:50437 )

♂ • most mice exhibit focal atrophic changes in the seminiferous tubules

reproductive system

increased prostate gland tumor incidence ( J:63478 )

♂

abnormal seminiferous tubule morphology ( J:50437 )

♂ • most mice exhibit focal atrophic changes in the seminiferous tubules

increased endometrial carcinoma incidence ( J:63478 )

♀ • 22% of females develop endometrial carcinoma, with the earliest case found at 30 weeks of age

endometrium hyperplasia ( J:63478 )

♀ • all females 26 weeks of age or older show endometrial hyperplasia

immune system

enlarged Peyer's patches ( J:63478 )

• enlarged Peyer's patches composed of lymphohistiocytic infiltrates

increased T cell derived lymphoma incidence ( J:50437 )

• 88% of the tumors are lymphoma/leukemia of the T-cell type

integument

increased mammary gland tumor incidence ( J:63478 )

• 4% of mutants aged 26-29 weeks, 61% aged 30-49 weeks and 83% aged 50-65 weeks develop breast tumors, indicating an increased incidence of breast cancer as mice age

increased fibroadenoma incidence ( J:63478 )

• small breast tumors are classified as fibroadenoma

increased mammary adenocarcinoma incidence ( J:63478 )

• 49% of females develop breast tumors, most classified as Dunn's adenocarcinoma type C

hematopoietic system

increased T cell derived lymphoma incidence ( J:50437 )

• 88% of the tumors are lymphoma/leukemia of the T-cell type

homeostasis/metabolism

increased incidence of tumors by ionizing radiation induction ( J:50437 )

• 19% of gamma-irradiated mutants develop tumors compared to none of wild-type

• tumors are thymic lymphomas/leukemias

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Cowden syndrome		DOID:6457	OMIM:PS158350	J:63478
Cowden syndrome 1		DOID:0050657	OMIM:158350	J:63478

Genotype
MGI:5569932

ht6

• Allelic Composition: Pten^tm1Rps/Pten⁺
• Genetic Background: involves: 129S1/Sv * 129S1/SvImJ * C57BL/6J

neoplasm

increased prostate intraepithelial neoplasia incidence ( J:75085 )

♂ • at 6 months of age, high-grade prostatic intraepithelial neoplasia/early carcinoma lesions are seen in 10% of prostates and by 12 months of age, 34% of prostates are still lesion-free

♂ • lesions show absence of Nkx3-1 protein expression

reproductive system

abnormal prostate gland epithelium morphology ( J:75085 )

♂ • prostates exhibit localized regions of severely dysplastic epithelium at 6 months of age

increased prostate intraepithelial neoplasia incidence ( J:75085 )

♂ • at 6 months of age, high-grade prostatic intraepithelial neoplasia/early carcinoma lesions are seen in 10% of prostates and by 12 months of age, 34% of prostates are still lesion-free

♂ • lesions show absence of Nkx3-1 protein expression

endocrine/exocrine glands

abnormal prostate gland epithelium morphology ( J:75085 )

♂ • prostates exhibit localized regions of severely dysplastic epithelium at 6 months of age

increased prostate intraepithelial neoplasia incidence ( J:75085 )

♂ • at 6 months of age, high-grade prostatic intraepithelial neoplasia/early carcinoma lesions are seen in 10% of prostates and by 12 months of age, 34% of prostates are still lesion-free

♂ • lesions show absence of Nkx3-1 protein expression

Genotype
MGI:2179045

ht7

• Allelic Composition: Pten^tm1Rps/Pten⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6J

Gut polyps and lymphoid hyperplasia in Pten^tm1Rps/Pten⁺ mice

mortality/aging

premature death ( J:53065 )

• about 12% of older mice ranging in age from 20-56 weeks die or were sacrificed due to morbidity

neoplasm

increased tumor incidence ( J:53065 )

• neoplasms in multiple organs including the endometrium, liver, prostate, gastrointestinal tract, thyroid, and thymus

• tumors of the gastrointestinal epithelium develop in association with gut lymphoid tissue

• tumors of the endometrium, thyroid, prostate, and liver are not associated with lymphoid tissue and appear highly mitotic

• the tumors that cause morbidity include lymphomas, synchronous thyroid carcinoma, liver adenoma, poorly differentiated leukemia and teratoma

increased thyroid carcinoma incidence ( J:53065 )

• thyroid carcinoma

increased prostate intraepithelial neoplasia incidence ( J:53065 )

♂ • 3 of 8 males at 6-22 weeks of age display prostatic intraepithelial neoplasia; an additional 3 mice have foci of benign epithelial hyperplasia in the prostate

increased liver adenoma incidence ( J:53065 )

increased leukemia incidence ( J:53065 )

• poorly differentiated leukemia

increased lymphoma incidence ( J:53065 )

• lymphomas develop in 7 of 256 mice that were clinically sick

• all mutants that develop lymphoma display diffuse microscopic infiltration of all organs by atypical immature lymphoid cells

increased teratoma incidence ( J:53065 )

digestive/alimentary system

intestine polyps ( J:53065 )

• intestinal polyps are seen in all mutants from 7 to 18 weeks of age; multiple polyps frequently cluster within a single region

• most polyps are lymphoid polyps with normal epithelium; the second most frequent type of polyp is lymphoid polyps with epithelial hyperplasia

endocrine/exocrine glands

enlarged thymus ( J:53065 )

• 5 of the 7 mutants that develop lymphoma have an enlarged thymus

abnormal thyroid gland morphology ( J:53065 )

• 3 of 20 mutants at 6-22 weeks of age display follicular or papillary noninvasive neoplasia of the thyroid and an additional 3 mice have atypical epithelial changes in the thyroid

increased thyroid carcinoma incidence ( J:53065 )

• thyroid carcinoma

increased prostate intraepithelial neoplasia incidence ( J:53065 )

♂ • 3 of 8 males at 6-22 weeks of age display prostatic intraepithelial neoplasia; an additional 3 mice have foci of benign epithelial hyperplasia in the prostate

hematopoietic system

enlarged thymus ( J:53065 )

• 5 of the 7 mutants that develop lymphoma have an enlarged thymus

enlarged spleen ( J:53065 )

• all mutants that develop lymphoma have splenomegaly

• by 50 weeks of age, all females and 45% of males have splenomegaly

immune system

enlarged thymus ( J:53065 )

• 5 of the 7 mutants that develop lymphoma have an enlarged thymus

enlarged spleen ( J:53065 )

• all mutants that develop lymphoma have splenomegaly

• by 50 weeks of age, all females and 45% of males have splenomegaly

abnormal lymph node B cell domain morphology ( J:53065 )

• in the hyperplastic lymph nodes and aggregates, follicular organization is blurred with mixing of the B and T cell regions

lymph node hyperplasia ( J:53065 )

• neoplastic hyperplasia of lymph nodes caused by a defect in apoptosis in B cells and macrophages

• expansion of the interfollicular areas, medullary cords, and residual follicular and paracortical hyperplasia composed of B, T, macrophage, and fibroblast cells

reproductive system

increased prostate intraepithelial neoplasia incidence ( J:53065 )

♂ • 3 of 8 males at 6-22 weeks of age display prostatic intraepithelial neoplasia; an additional 3 mice have foci of benign epithelial hyperplasia in the prostate

endometrium hyperplasia ( J:53065 )

♀ • 100% of females aged 18-39 weeks display multifocal endometrial complex atypical hyperplasia, a lesion that is a precursor of endometrial carcinoma

growth/size/body

enlarged spleen ( J:53065 )

• all mutants that develop lymphoma have splenomegaly

• by 50 weeks of age, all females and 45% of males have splenomegaly

liver/biliary system

increased liver adenoma incidence ( J:53065 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Cowden syndrome		DOID:6457	OMIM:PS158350	J:53065
Cowden syndrome 1		DOID:0050657	OMIM:158350	J:53065

Genotype
MGI:2179025

ht8

• Allelic Composition: Pten^tm1Ppp/Pten⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6J

neoplasm

increased malignant tumor incidence ( J:49532 )

• increased incidence of malignant tumors of various histological origins; age of incidence beginning at 6 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Cowden syndrome		DOID:6457	OMIM:PS158350	J:49532
Cowden syndrome 1		DOID:0050657	OMIM:158350	J:49532

Genotype
MGI:3707147

ht9

• Allelic Composition: Pten^tm1Hwu/Pten⁺
• Genetic Background: involves: 129S4/SvJae * BALB/c

neoplasm

abnormal tumor incidence ( J:110567 )

• Background Sensitivity: spectrum of tumor incidence and onset on the BALB/c background are similar to Pten^tm1.1Hwu on the BALB/c background in the first seven months

Genotype
MGI:3707124

ht10

• Allelic Composition: Pten^tm2Hwu/Pten⁺
• Genetic Background: involves: 129S4/SvJae * BALB/c

neoplasm

abnormal tumor incidence ( J:110567 )

• Background Sensitivity: spectrum of tumor incidence and onset on the BALB/c background are similar to Pten^tm1.1Hwu on the BALB/c background in the first seven months

Genotype
MGI:3707122

ht11

• Allelic Composition: Pten^tm1.1Hwu/Pten⁺
• Genetic Background: involves: 129S4/SvJae * BALB/c

neoplasm

abnormal metastatic potential ( J:110567 )

• most of the tumor seen are benign and isolated, but in three cases malignant transformation was observed; in two mice, local invasion occurred while in one, whole body metastasis occurred

abnormal tumor incidence ( J:110567 )

• onset of tumor formation on the BALB/c background is delayed compared to that reported on other backgrounds; 90% of heterozygotes are tumor-free for their first 6 months, and only 50% have developed tumors by 10 months of age

• Background Sensitivity: 9% of aged 7-14 month old females show endometrial hyperplasia on this background

increased mammary adenocarcinoma incidence ( J:110567 )

• 30% of females develop mammary tumors ranging from 1-10 tumors per animal

increased prostate gland tumor incidence ( J:110567 )

♂ • 95% of male mice aged 10-15 months display prostate abnormalities ranging from hyperplasia to local invasion

increased hemangioma incidence ( J:110567 )

• 45% of female uteri have hemangioma lesions at 7-14 months; these masses consist of aggregates of endothelium-lined blood filled spaces of variable sizes

• in some areas, tissue resembled arterioles or venules, while at edges of large spaces, there are small capillary aggregates; smaller vessels are packed with erythrocytes

• vascular abnormalities are also found in the brain, mammary glands, spinal cord or body walls of some heterozygotes, but at lower frequencies than in the uterus

cardiovascular system

abnormal brain vasculature morphology ( J:110567 )

• similar lesions to those in the uterus are occasionally observed in the brain of some mice at 14 months

• in a male at 14 months, the lesions of the cerebrum and olfactory bulb were aggregates of endothelium-lined, cavernous blood-filled spaces separated by narrow connective-tissue septa; blood in some spaces was thrombosed and calcified

• aggregates of capillary arteriole- and venule-like vessels similar to the ones in the uteri are observed

reproductive system

increased prostate gland tumor incidence ( J:110567 )

♂ • 95% of male mice aged 10-15 months display prostate abnormalities ranging from hyperplasia to local invasion

abnormal uterus morphology ( J:110567 )

♀ • hemangiomas are predominantly in the myometrium, involve the whole uterine wall, and protrude into the uterine lumen

immune system

lymphoid hyperplasia ( J:110567 )

• incidence of lymphoid hyperplasia or neoplasia is 25%

nervous system

abnormal brain vasculature morphology ( J:110567 )

• similar lesions to those in the uterus are occasionally observed in the brain of some mice at 14 months

• in a male at 14 months, the lesions of the cerebrum and olfactory bulb were aggregates of endothelium-lined, cavernous blood-filled spaces separated by narrow connective-tissue septa; blood in some spaces was thrombosed and calcified

• aggregates of capillary arteriole- and venule-like vessels similar to the ones in the uteri are observed

abnormal olfactory bulb morphology ( J:110567 )

• in a male at 14 months, the left olfactory bulb and frontal lobes of the cerebrum seem to be replaced by masses of hemorrhagic-appearing tissue; the mouse seemed ataxic, with enlargement of the forehead

integument

increased mammary adenocarcinoma incidence ( J:110567 )

• 30% of females develop mammary tumors ranging from 1-10 tumors per animal

endocrine/exocrine glands

increased mammary adenocarcinoma incidence ( J:110567 )

• 30% of females develop mammary tumors ranging from 1-10 tumors per animal

increased prostate gland tumor incidence ( J:110567 )

♂ • 95% of male mice aged 10-15 months display prostate abnormalities ranging from hyperplasia to local invasion

Genotype
MGI:3707123

ht12

• Allelic Composition: Pten^tm1.1Hwu/Pten⁺
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

neoplasm

abnormal tumor incidence ( J:110567 )

• Background Sensitivity: 25% of aged 7-14 month old F2 females show endometrial hyperplasia compared to 9% on 129/BALB/c background

Genotype
MGI:3707125

ht13

• Allelic Composition: Pten^tm2Hwu/Pten⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

neoplasm

abnormal tumor incidence ( J:110567 )

• Background Sensitivity: tumor incidence is about 9-fold higher on C57BL/6 background than on 129/BALB/c background

Genotype
MGI:5008590

ht14

• Allelic Composition: Pten^tm1.1Hwu/Pten⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6NTac

neoplasm

increased thyroid adenoma incidence ( J:170965 )

increased lymphoma incidence ( J:170965 )

• at 6 to 7 months of age

endocrine/exocrine glands

increased thyroid adenoma incidence ( J:170965 )

Genotype
MGI:6512404

ht15

• Allelic Composition: Pten^tm1.2Mwst/Pten⁺
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss * FVB/N

reproductive system

increased prostate gland tumor incidence ( J:158751 )

♂ • 93.3% of mice develop proliferative lesions of the prostate

♂ • increased coincidence with stomach tumors

increased uterus carcinoma incidence ( J:158751 )

♀ • proliferative lesions of the endometrium, simple hyperplasia and atypical hyperplasia

♀ • increased coincidence with lymph node neoplasms

endometrium hyperplasia ( J:158751 )

♀ • proliferative lesions of the endometrium, simple hyperplasia and atypical hyperplasia

digestive/alimentary system

increased gastrointestinal tumor incidence ( J:158751 )

• 19.1% of 9 month old mice develop proliferative lesions of the intestine

increased stomach tumor incidence ( J:158751 )

• increased coincidence of stomach tumors with prostate neoplasms

neoplasm

increased gastrointestinal tumor incidence ( J:158751 )

• 19.1% of 9 month old mice develop proliferative lesions of the intestine

increased stomach tumor incidence ( J:158751 )

• increased coincidence of stomach tumors with prostate neoplasms

increased adrenal gland tumor incidence ( J:158751 )

• in 76.5% of 9 month old mice, with a male bias

increased thyroid tumor incidence ( J:158751 )

• 76.3% of 9 month old mice develop proliferative lesions of the thyroid

• increased coincidence of thyroid tumors with lymph node neoplasms

increased mammary gland tumor incidence ( J:158751 )

• mammary intraepithelial neoplasia and invasive carcinoma in female mice

• increased coincidence with lymph node neoplasms in female mice

increased mammary adenoacanthoma incidence ( J:158751 )

• adenosquamous carcinoma in female mice

increased prostate gland tumor incidence ( J:158751 )

♂ • 93.3% of mice develop proliferative lesions of the prostate

♂ • increased coincidence with stomach tumors

increased lymphoma incidence ( J:158751 )

• 58.9% of mice develop proliferative lesions of the lymph node, with a female bias

• increased coincidence with uterine neoplasms

• increased coincidence with mammary gland neoplasms

• increased coincidence of thyroid tumors with lymph node neoplasms

increased T cell derived lymphoma incidence ( J:158751 )

• 55.8% of 9 month old mice develop proliferative lesions of the thymus

increased uterus carcinoma incidence ( J:158751 )

♀ • proliferative lesions of the endometrium, simple hyperplasia and atypical hyperplasia

♀ • increased coincidence with lymph node neoplasms

integument

increased mammary gland tumor incidence ( J:158751 )

• mammary intraepithelial neoplasia and invasive carcinoma in female mice

• increased coincidence with lymph node neoplasms in female mice

increased mammary adenoacanthoma incidence ( J:158751 )

• adenosquamous carcinoma in female mice

endocrine/exocrine glands

increased adrenal gland tumor incidence ( J:158751 )

• in 76.5% of 9 month old mice, with a male bias

increased T cell derived lymphoma incidence ( J:158751 )

• 55.8% of 9 month old mice develop proliferative lesions of the thymus

increased thyroid tumor incidence ( J:158751 )

• 76.3% of 9 month old mice develop proliferative lesions of the thyroid

• increased coincidence of thyroid tumors with lymph node neoplasms

increased mammary gland tumor incidence ( J:158751 )

• mammary intraepithelial neoplasia and invasive carcinoma in female mice

• increased coincidence with lymph node neoplasms in female mice

increased mammary adenoacanthoma incidence ( J:158751 )

• adenosquamous carcinoma in female mice

increased prostate gland tumor incidence ( J:158751 )

♂ • 93.3% of mice develop proliferative lesions of the prostate

♂ • increased coincidence with stomach tumors

immune system

increased T cell derived lymphoma incidence ( J:158751 )

• 55.8% of 9 month old mice develop proliferative lesions of the thymus

hematopoietic system

increased T cell derived lymphoma incidence ( J:158751 )

• 55.8% of 9 month old mice develop proliferative lesions of the thymus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Cowden syndrome		DOID:6457	OMIM:PS158350	J:158751

Genotype
MGI:4442333

ht16

• Allelic Composition: Pten^tm1.1Gle/Pten⁺
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss * FVB/N

neoplasm

increased stomach tumor incidence ( J:158751 )

• increased coincidence of stomach tumors with prostate neoplasms

increased adrenal gland tumor incidence ( J:158751 )

• 51.6% of 9 month old mice develop proliferative lesions of the adrenal gland

increased thyroid tumor incidence ( J:158751 )

• 58.6% of 9 month old mice develop proliferative lesions of the thyroid

increased mammary gland tumor incidence ( J:158751 )

• increased coincidence of mammary tumor in females and intestinal lesions

• increased coincidence of mammary tumor in females and adrenal lesions

increased prostate gland tumor incidence ( J:158751 )

♂ • increased coincidence of stomach tumors with prostate neoplasms

increased lymphoma incidence ( J:158751 )

• 54.1% of 9 month old mice develop proliferative lesions of the lymph node

increased T cell derived lymphoma incidence ( J:158751 )

• 65.0% of 9 month old mice develop proliferative lesions of the thymus

reproductive system

increased prostate gland tumor incidence ( J:158751 )

♂ • increased coincidence of stomach tumors with prostate neoplasms

endometrium hyperplasia ( J:158751 )

♀ • proliferative lesions of the endometrium, simple hyperplasia and atypical hyperplasia

integument

increased mammary gland tumor incidence ( J:158751 )

• increased coincidence of mammary tumor in females and intestinal lesions

• increased coincidence of mammary tumor in females and adrenal lesions

endocrine/exocrine glands

increased adrenal gland tumor incidence ( J:158751 )

• 51.6% of 9 month old mice develop proliferative lesions of the adrenal gland

increased T cell derived lymphoma incidence ( J:158751 )

• 65.0% of 9 month old mice develop proliferative lesions of the thymus

increased thyroid tumor incidence ( J:158751 )

• 58.6% of 9 month old mice develop proliferative lesions of the thyroid

increased mammary gland tumor incidence ( J:158751 )

• increased coincidence of mammary tumor in females and intestinal lesions

• increased coincidence of mammary tumor in females and adrenal lesions

increased prostate gland tumor incidence ( J:158751 )

♂ • increased coincidence of stomach tumors with prostate neoplasms

digestive/alimentary system

increased stomach tumor incidence ( J:158751 )

• increased coincidence of stomach tumors with prostate neoplasms

immune system

increased T cell derived lymphoma incidence ( J:158751 )

• 65.0% of 9 month old mice develop proliferative lesions of the thymus

hematopoietic system

increased T cell derived lymphoma incidence ( J:158751 )

• 65.0% of 9 month old mice develop proliferative lesions of the thymus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Cowden syndrome		DOID:6457	OMIM:PS158350	J:158751

Genotype
MGI:4442335

ht17

• Allelic Composition: Pten^tm2.1Gle/Pten⁺
• Genetic Background: involves: 129S6/SvEvTac * Black Swiss * FVB/N

neoplasm

increased adrenal gland tumor incidence ( J:158751 )

• 70.7% of 9 month old mice develop proliferative lesions of the adrenal gland

increased thyroid tumor incidence ( J:158751 )

• 81.6% of 9 month old mice develop proliferative lesions of the thyroid

increased mammary gland tumor incidence ( J:158751 )

• mammary intraepithelial neoplasia in females

• females develop large palpable tumors with adenosquamous morphology and a prominent stromal component

• increased coincidence in females of mammary tumor and lymph node neoplasms

• a few males develop high grade mammary intraepithelial neoplasia

increased mammary adenoacanthoma incidence ( J:158751 )

• adenosquamous carcinoma

increased prostate gland tumor incidence ( J:158751 )

♂ • 86.4% of 9 month old mice develop proliferative lesions of the prostate

increased lymphoma incidence ( J:158751 )

• 55.8% of 9 month old mice develop proliferative lesions of the lymph node

• increased coincidence of lymph node neoplasms and mammary tumors in females

increased T cell derived lymphoma incidence ( J:158751 )

• 59.5% of 9 month old mice develop proliferative lesions of the thymus

endocrine/exocrine glands

increased adrenal gland tumor incidence ( J:158751 )

• 70.7% of 9 month old mice develop proliferative lesions of the adrenal gland

increased T cell derived lymphoma incidence ( J:158751 )

• 59.5% of 9 month old mice develop proliferative lesions of the thymus

abnormal thyroid follicular cell morphology ( J:158751 )

• thyroid follicular lesions

increased thyroid tumor incidence ( J:158751 )

• 81.6% of 9 month old mice develop proliferative lesions of the thyroid

increased mammary gland tumor incidence ( J:158751 )

• mammary intraepithelial neoplasia in females

• females develop large palpable tumors with adenosquamous morphology and a prominent stromal component

• increased coincidence in females of mammary tumor and lymph node neoplasms

• a few males develop high grade mammary intraepithelial neoplasia

increased mammary adenoacanthoma incidence ( J:158751 )

• adenosquamous carcinoma

increased prostate gland tumor incidence ( J:158751 )

♂ • 86.4% of 9 month old mice develop proliferative lesions of the prostate

reproductive system

increased prostate gland tumor incidence ( J:158751 )

♂ • 86.4% of 9 month old mice develop proliferative lesions of the prostate

endometrium hyperplasia ( J:158751 )

♀ • proliferative lesions of the endometrium, simple hyperplasia and atypical hyperplasia

integument

increased mammary gland tumor incidence ( J:158751 )

• mammary intraepithelial neoplasia in females

• females develop large palpable tumors with adenosquamous morphology and a prominent stromal component

• increased coincidence in females of mammary tumor and lymph node neoplasms

• a few males develop high grade mammary intraepithelial neoplasia

increased mammary adenoacanthoma incidence ( J:158751 )

• adenosquamous carcinoma

immune system

increased T cell derived lymphoma incidence ( J:158751 )

• 59.5% of 9 month old mice develop proliferative lesions of the thymus

hematopoietic system

increased T cell derived lymphoma incidence ( J:158751 )

• 59.5% of 9 month old mice develop proliferative lesions of the thymus

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Cowden syndrome		DOID:6457	OMIM:PS158350	J:158751

Genotype
MGI:5509200

ht18

• Allelic Composition: Pten^tm1Engc/Pten⁺
• Genetic Background: involves: CD-1

cellular

abnormal cell physiology ( J:197051 )

• increased proteasome activity and protein ubiquitination in brain tissue

Genotype
MGI:5812675

ht19

• Allelic Composition: Pten^tm1.1Mro/Pten⁺
• Genetic Background: Not Specified

endocrine/exocrine glands

increased pheochromocytoma incidence ( J:236514 )

• at 10 months of age, 73% of mice develop a pheochromocytoma

• tumors do not show accumulation of succinate

neoplasm

increased pheochromocytoma incidence ( J:236514 )

• at 10 months of age, 73% of mice develop a pheochromocytoma

• tumors do not show accumulation of succinate

increased metastatic potential ( J:236514 )

• lung micro-metastasis are seen in 64% of mice

Genotype
MGI:5517709

cn20

• Allelic Composition: Pten^tm1Hwu/Pten⁺; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: B6.Cg-Pten^tm1Hwu Tg(Nkx2-1-cre)2Sand

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:197590 )

• altered thyroid structure with normal areas that include colloid-filled follicles and normal areas with focal hyperplasia, polynuclear cells, small nonencapsulated areas of hypercellularity with solid and/or mircofollicular patterns and internal hemorrhage

increased thyroid tumor incidence ( J:197590 )

• 100% of mutants develop differentiated follicular tumors of the thyroid after about 2 years of age

homeostasis/metabolism

decreased thyroxine level ( J:197590 )

• P14 mutants show a mild decrease of T4 but normal TSH

neoplasm

increased thyroid tumor incidence ( J:197590 )

• 100% of mutants develop differentiated follicular tumors of the thyroid after about 2 years of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
follicular thyroid carcinoma		DOID:3962	OMIM:188470	J:197590

Genotype
MGI:5467305

cn21

• 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

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 )

♂ • 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

endocrine/exocrine glands

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

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

Genotype
MGI:5902136

cn22

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

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

Genotype
MGI:5543907

cn23

• 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

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:6256732

cn24

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm2Mak/Pten⁺; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA

neoplasm

increased cholangiocarcinoma incidence ( J:254370 )

• some lesions are diagnosed as intrahepatic cholangiocarcinoma by the appearance of adenocarcinoma showing tubular and/or papillary structures with a fibrous stroma; these tumor cells show loss of Pten expression

increased liver tumor incidence ( J:254370 )

• mice develop liver tumors at 6 months of age, showing obvious symptoms after 7 months with abdominal distension due to multiple tumors at later stages

• mice develop liver tumors with both hepatocyte and cholangiocyte differentiation

increased hepatocellular carcinoma incidence ( J:254370 )

• majority of large nodules are hepatocellular dysplasia, a precursor lesion of hepatocellular carcinoma

liver/biliary system

increased cholangiocarcinoma incidence ( J:254370 )

• some lesions are diagnosed as intrahepatic cholangiocarcinoma by the appearance of adenocarcinoma showing tubular and/or papillary structures with a fibrous stroma; these tumor cells show loss of Pten expression

increased liver tumor incidence ( J:254370 )

• mice develop liver tumors at 6 months of age, showing obvious symptoms after 7 months with abdominal distension due to multiple tumors at later stages

• mice develop liver tumors with both hepatocyte and cholangiocyte differentiation

increased hepatocellular carcinoma incidence ( J:254370 )

• majority of large nodules are hepatocellular dysplasia, a precursor lesion of hepatocellular carcinoma

endocrine/exocrine glands

increased cholangiocarcinoma incidence ( J:254370 )

• some lesions are diagnosed as intrahepatic cholangiocarcinoma by the appearance of adenocarcinoma showing tubular and/or papillary structures with a fibrous stroma; these tumor cells show loss of Pten expression

Genotype
MGI:3831280

cn25

• 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

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)

Genotype
MGI:5427498

cn26

• Allelic Composition: Gt(ROSA)26Sor^{tm1(CAG-Bmi1,-EGFP)Nki}/Gt(ROSA)26Sor⁺; Pten^tm1Mro/Pten⁺; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2 * FVB/N

Prostate cancer progression in Tg(Pbsn-cre)4Prb/0 Gt(ROSA)26Sor^{tm1(CAG-Bmi1,-EGFP)Nki}/Gt(ROSA)26Sor⁺, Tg(Pbsn-cre)4Prb/0 Pten^tm1Mro/Pten⁺, and Tg(Pbsn-cre)4Prb/0 Gt(ROSA)26Sor^{tm1(CAG-Bmi1,-EGFP)Nki}/Gt(ROSA)26Sor⁺ Pten^tm1Mro/Pten⁺ mice

neoplasm

increased prostate gland adenocarcinoma incidence ( J:184533 )

♂ • 55% penetrance at 1 year

♂ • multifocal, predominantly localized in the dorsolateral lobe that are locally invasive and highly vascularized

increased prostate intraepithelial neoplasia incidence ( J:184533 )

♂ • at 6 months

renal/urinary system

urinary bladder obstruction ( J:184533 )

• frequently

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:184533 )

♂ • 55% penetrance at 1 year

♂ • multifocal, predominantly localized in the dorsolateral lobe that are locally invasive and highly vascularized

increased prostate intraepithelial neoplasia incidence ( J:184533 )

♂ • at 6 months

reproductive system

increased prostate gland adenocarcinoma incidence ( J:184533 )

♂ • 55% penetrance at 1 year

♂ • multifocal, predominantly localized in the dorsolateral lobe that are locally invasive and highly vascularized

increased prostate intraepithelial neoplasia incidence ( J:184533 )

♂ • at 6 months

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:184533

Genotype
MGI:3761927

cn27

• Allelic Composition: Pten^tm1Mro/Pten⁺; Tg(KLK3-cre)D4Trp/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

reproductive system

abnormal prostate gland epithelium morphology ( J:99524 )

♂ • at 4-5 months, epithelial cell lining of prostate tubules is disorganized, with tufting and/or cribriform growth patterns, unlike the regularly-layered columnar epithelial lining in controls

♂ • epithelial cells are generally enlarged with some foci showing dysplasia characterized by cells with dense cytoplasm enlarged, somewhat vesicular nuclei with conspicuous nuclei

♂ • at 7-9 months, distention of glands continues, with dysplasia becoming more diffuse

increased prostate gland weight ( J:99524 )

♂ • prostate lobes are obviously enlarged compared with control prostates; at 4-5 months, average weight is increased 2-fold and at 7-9 months increase is 3-fold

♂ • at 14 months with prostate cancer, weight has rapidly increased

prostate gland hyperplasia ( J:99524 )

♂ • at 4-5 months of age, most glands of the different lobes show hyperplasia with accumulation of luminal cells, with distension of individual preexisting glands

♂ • at 7-9 months hyperplasia continues to progress

increased prostate gland tumor incidence ( J:99524 )

♂ • progressive tumor development is observed in mice at 4-5 months along with focal prostatic intraepithelial neoplasia (PIN) lesions, 7-9 months with more widespread PIN and focal microinvasion and at 10-14 months with invasive tumors

♂ • in 14-month old mice, tumors are all shown to be epithelial in origin, classified as adenocarcinoma of poor, low or moderate grade differentiation

increased prostate gland adenocarcinoma incidence ( J:99524 )

♂

increased prostate intraepithelial neoplasia incidence ( J:99524 )

♂

endocrine/exocrine glands

abnormal prostate gland epithelium morphology ( J:99524 )

♂ • at 4-5 months, epithelial cell lining of prostate tubules is disorganized, with tufting and/or cribriform growth patterns, unlike the regularly-layered columnar epithelial lining in controls

♂ • epithelial cells are generally enlarged with some foci showing dysplasia characterized by cells with dense cytoplasm enlarged, somewhat vesicular nuclei with conspicuous nuclei

♂ • at 7-9 months, distention of glands continues, with dysplasia becoming more diffuse

increased prostate gland weight ( J:99524 )

♂ • prostate lobes are obviously enlarged compared with control prostates; at 4-5 months, average weight is increased 2-fold and at 7-9 months increase is 3-fold

♂ • at 14 months with prostate cancer, weight has rapidly increased

prostate gland hyperplasia ( J:99524 )

♂ • at 4-5 months of age, most glands of the different lobes show hyperplasia with accumulation of luminal cells, with distension of individual preexisting glands

♂ • at 7-9 months hyperplasia continues to progress

increased prostate gland tumor incidence ( J:99524 )

♂ • progressive tumor development is observed in mice at 4-5 months along with focal prostatic intraepithelial neoplasia (PIN) lesions, 7-9 months with more widespread PIN and focal microinvasion and at 10-14 months with invasive tumors

♂ • in 14-month old mice, tumors are all shown to be epithelial in origin, classified as adenocarcinoma of poor, low or moderate grade differentiation

increased prostate gland adenocarcinoma incidence ( J:99524 )

♂

increased prostate intraepithelial neoplasia incidence ( J:99524 )

♂

neoplasm

increased prostate gland tumor incidence ( J:99524 )

♂ • progressive tumor development is observed in mice at 4-5 months along with focal prostatic intraepithelial neoplasia (PIN) lesions, 7-9 months with more widespread PIN and focal microinvasion and at 10-14 months with invasive tumors

♂ • in 14-month old mice, tumors are all shown to be epithelial in origin, classified as adenocarcinoma of poor, low or moderate grade differentiation

increased prostate gland adenocarcinoma incidence ( J:99524 )

♂

increased prostate intraepithelial neoplasia incidence ( J:99524 )

♂

Genotype
MGI:4840094

cn28

• Allelic Composition: Nf1^tm1Par/Nf1⁺; Pten^tm1Hwu/Pten⁺; Trp53^tm1Tyj/Trp53⁺; Tg(GFAP-cre)25Mes/0
• Genetic Background: involves: 129S1/Sv * 129S2/SvPas * 129S4/SvJae * 129X1/SvJ * FVB/N

mortality/aging

premature death ( J:134611 )

• most die as early as 10 weeks of age, and usually within a week of showing signs of morbidity

behavior/neurological

increased startle reflex ( J:134611 )

• exaggerated startle response

ataxia ( J:134611 )

• ataxic gait

unidirectional circling ( J:134611 )

seizures ( J:134611 )

• generalized motor seizures

nervous system

seizures ( J:134611 )

• generalized motor seizures

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• gliomas from asymptomatic mutants are primarily classified as grade 3 astocytomas

• 5-fold higher growth rate of astrocytomas compared with tumors from transgenic mice heterozygous for Nf1^tm1Par and Trp53^tm1Tyj and hemizygous for Tg(GFAP-cre)25Mes

neoplasm

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• gliomas from asymptomatic mutants are primarily classified as grade 3 astocytomas

• 5-fold higher growth rate of astrocytomas compared with tumors from transgenic mice heterozygous for Nf1^tm1Par and Trp53^tm1Tyj and hemizygous for Tg(GFAP-cre)25Mes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant astrocytoma		DOID:3069		J:134611

Genotype
MGI:4849443

cn29

• Allelic Composition: Nf1^tm1Par/Nf1⁺; Pten^tm1Hwu/Pten⁺; Tg(Gfap-cre)77.6Mvs/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6NHsd

neoplasm

neoplasm ( J:154673 )

N • mutants do not develop tumors

Genotype
MGI:4839508

cn30

• Allelic Composition: Erbb2^{tm8(Erbb2)Mul}/Erbb2⁺; Pten^tm1Hwu/Pten⁺; Tg(MMTV-cre)7Mul/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N

neoplasm

increased mammary gland tumor incidence ( J:133305 )

• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 6.5 compared with 15.3 months

• tumor progression is associated with loss of heterozygosity at the Pten locus in 50% of mutant mammary tumors

• tumors are similar to basal-like subtype of human breast cancer

increased metastatic potential ( J:133305 )

• 35% incidence of lung metastases compared with 5% in single Erbb2 mutants

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:133305 )

• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 6.5 compared with 15.3 months

• tumor progression is associated with loss of heterozygosity at the Pten locus in 50% of mutant mammary tumors

• tumors are similar to basal-like subtype of human breast cancer

integument

increased mammary gland tumor incidence ( J:133305 )

• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 6.5 compared with 15.3 months

• tumor progression is associated with loss of heterozygosity at the Pten locus in 50% of mutant mammary tumors

• tumors are similar to basal-like subtype of human breast cancer

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:133305

Genotype
MGI:4840096

cn31

• Allelic Composition: Nf1^tm1Par/Nf1⁺; Pten^tm1Hwu/Pten⁺; Trp53^tm1Elee/Trp53⁺; Tg(GFAP-cre)25Mes/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N

mortality/aging

premature death ( J:134611 )

• most die as early as 10 weeks of age, and usually within a week of showing signs of morbidity

behavior/neurological

increased startle reflex ( J:134611 )

• exaggerated startle response

ataxia ( J:134611 )

• ataxic gait

unidirectional circling ( J:134611 )

seizures ( J:134611 )

• generalized motor seizures

nervous system

seizures ( J:134611 )

• generalized motor seizures

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• mutants develop astrocytomas

• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci

neoplasm

increased brain tumor incidence ( J:134611 )

increased astrocytoma incidence ( J:134611 )

• mutants develop astrocytomas

• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci

Genotype
MGI:3783573

cn32

• Allelic Composition: Bcl2l11^tm1.1Ast/Bcl2l11⁺; Pten^tm1Hwu/Pten⁺; Tg(CD2-icre)4Kio/0
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * C57BL/10 * CBA/Ca

immune system

increased germinal center B cell number ( J:133215 )

• at 20 to 28 weeks of age, mice exhibit increased germinal center B cell number compared to controls but not as much as in Gt(ROSA)26Sor^tm3Rsky/Gt(ROSA)26Sor^tm3Rsky/ Tg(CD2-cre)1Kio mice

abnormal T cell number ( J:133215 )

• at 20 to 28 weeks of age, mice accumulate more antigen-experienced T cells than in control mice but not as much as in Gt(ROSA)26Sor^tm3Rsky/Gt(ROSA)26Sor^tm3Rsky/ Tg(CD2-cre)1Kio mice

hematopoietic system

increased germinal center B cell number ( J:133215 )

• at 20 to 28 weeks of age, mice exhibit increased germinal center B cell number compared to controls but not as much as in Gt(ROSA)26Sor^tm3Rsky/Gt(ROSA)26Sor^tm3Rsky/ Tg(CD2-cre)1Kio mice

abnormal T cell number ( J:133215 )

• at 20 to 28 weeks of age, mice accumulate more antigen-experienced T cells than in control mice but not as much as in Gt(ROSA)26Sor^tm3Rsky/Gt(ROSA)26Sor^tm3Rsky/ Tg(CD2-cre)1Kio mice

Genotype
MGI:5897775

cn33

• Allelic Composition: Prkar1a^tm1.2Lsk/Prkar1a⁺; Pten^tm1.1Mwst/Pten⁺; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * FVB/NCr

mortality/aging

decreased survivor rate ( J:225245 )

• mice exhibit reduced survival compared to single heterozygotes

neoplasm

neoplasm ( J:225245 )

N • mice do not show increased incidence of thyroid cancer

Genotype
MGI:6275174

cn34

• 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

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

Genotype
MGI:5485415

cn35

• 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

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)

Genotype
MGI:5812679

cn36

• Allelic Composition: Pten^tm1Mro/Pten⁺; Sdhb^tm1.1Ics/Sdhb⁺; Tg(KLK3-cre)D4Trp/0
• Genetic Background: involves: 129S2/SvPas * FVB

endocrine/exocrine glands

increased pheochromocytoma incidence ( J:236514 )

• 64% of mice develop pheochromocytoma

neoplasm

increased pheochromocytoma incidence ( J:236514 )

• 64% of mice develop pheochromocytoma

Genotype
MGI:5013916

cn37

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten⁺; Tg(Pdx1-cre)89.1Dam/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

neoplasm

increased pancreas tumor incidence ( J:164210 )

• mutants exhibit accelerated development of acinar-to-ductal metaplasia, malignant pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma compared to single heterozygous Kras mutants, with almost 100% of mutants succumbing to cancer by 12 months of age

• 21 of 25 mice alive past 2 months of age develop well-to-moderately differentiated invasive ductal cancers

• rare metastasis to lungs is seen

increased pancreatic ductal adenocarcinoma incidence ( J:164210 )

• at 3 months of age, 8 of 12 mutants show development of pancreatic ductal adenocarcinoma (PDAC), and all mice show PDAC by 6 months of age

• loss of Pten heterozygosity is seen during pancreatic ductal adenocarcinoma progression but not in mPanIN lesions

increased pancreatic intraepithelial neoplasia incidence ( J:164210 )

• mutants show malignant pancreatic intraepithelial neoplasia (mPanIN) development starting at 1 month of age, and all show mPanIN by 3 months of age

mortality/aging

premature death ( J:164210 )

• median survival time is about 3.5 months

endocrine/exocrine glands

increased pancreas tumor incidence ( J:164210 )

• mutants exhibit accelerated development of acinar-to-ductal metaplasia, malignant pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma compared to single heterozygous Kras mutants, with almost 100% of mutants succumbing to cancer by 12 months of age

• 21 of 25 mice alive past 2 months of age develop well-to-moderately differentiated invasive ductal cancers

• rare metastasis to lungs is seen

increased pancreatic ductal adenocarcinoma incidence ( J:164210 )

• at 3 months of age, 8 of 12 mutants show development of pancreatic ductal adenocarcinoma (PDAC), and all mice show PDAC by 6 months of age

• loss of Pten heterozygosity is seen during pancreatic ductal adenocarcinoma progression but not in mPanIN lesions

increased pancreatic intraepithelial neoplasia incidence ( J:164210 )

• mutants show malignant pancreatic intraepithelial neoplasia (mPanIN) development starting at 1 month of age, and all show mPanIN by 3 months of age

pancreatic acinar-to-ductal metaplasia ( J:164210 )

• acinar-to-ductal metaplasia is seen at 1-3 months of age, concentrated in the transition zone between morphologically normal pancreatic structures and mPanIN and PDAC lesions

• acinar-to-ductal metaplasia development precedes mPanIN formation

• metaplastic lesions show an increase in CD44+ cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pancreatic carcinoma		DOID:4905	OMIM:260350	J:164210

Genotype
MGI:5517675

cn38

• Allelic Composition: Pten^tm1Hwu/Pten⁺; Tg(Nkx2-1-cre)2Sand/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6

endocrine/exocrine glands

abnormal thyroid follicle morphology ( J:197590 )

• enlarged follicles

enlarged thyroid gland ( J:197590 )

• mutants have an enlarged thyroid at 2 years of age and exhibit a goiter-like phenotype, but do not show development of tumors

thyroid gland hyperplasia ( J:197590 )

homeostasis/metabolism

increased thyroxine level ( J:197590 )

• P14 mutants show an increase in T4 levels

Genotype
MGI:4420975

cn39

• Allelic Composition: Pten^tm1Hwu/Pten⁺; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2

neoplasm

increased prostate intraepithelial neoplasia incidence ( J:93902 )

♂ • latency to prostate intraepithelial neoplasia is 8 to 10 months

endocrine/exocrine glands

increased prostate intraepithelial neoplasia incidence ( J:93902 )

♂ • latency to prostate intraepithelial neoplasia is 8 to 10 months

reproductive system

increased prostate intraepithelial neoplasia incidence ( J:93902 )

♂ • latency to prostate intraepithelial neoplasia is 8 to 10 months

Genotype
MGI:4843916

cn40

• Allelic Composition: Pten^tm1Hwu/Pten⁺; Tg(ARR2/Pbsn-FGF8)3Prb/0; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2

endocrine/exocrine glands

prostate gland epithelial hyperplasia ( J:106650 )

♂

enlarged prostate gland ( J:106650 )

♂ • enlarged prostate gland due to epithelial hyperplasia

increased prostate gland adenocarcinoma incidence ( J:106650 )

♂ • prostatic adenocarcinomas are seen from 9 months onward

♂ • adenocarcinomas are seen in all lobes, although more often in the dorsolateral and ventral lobes than anterior lobes

♂ • 6 of 17 mutants at 9-16.2 months of age and 9 of 10 mutants at 18.2-19.1 months exhibit adenocarcinomas

♂ • adenocarcinomas show loss of heterozygosity of Pten

♂ • 2 of 31 mutants develop a rare form of mucinous adenocarcinoma

increased prostate intraepithelial neoplasia incidence ( J:106650 )

♂ • males by 6.5 months of age exhibit hyperplasia and focal-low grade PIN lesions in the prostate

♂ • males older than 7.5 months of age exhibit high-grade PINs

reproductive system

prostate gland epithelial hyperplasia ( J:106650 )

♂

enlarged prostate gland ( J:106650 )

♂ • enlarged prostate gland due to epithelial hyperplasia

increased prostate gland adenocarcinoma incidence ( J:106650 )

♂ • prostatic adenocarcinomas are seen from 9 months onward

♂ • adenocarcinomas are seen in all lobes, although more often in the dorsolateral and ventral lobes than anterior lobes

♂ • 6 of 17 mutants at 9-16.2 months of age and 9 of 10 mutants at 18.2-19.1 months exhibit adenocarcinomas

♂ • adenocarcinomas show loss of heterozygosity of Pten

♂ • 2 of 31 mutants develop a rare form of mucinous adenocarcinoma

increased prostate intraepithelial neoplasia incidence ( J:106650 )

♂ • males by 6.5 months of age exhibit hyperplasia and focal-low grade PIN lesions in the prostate

♂ • males older than 7.5 months of age exhibit high-grade PINs

neoplasm

increased prostate gland adenocarcinoma incidence ( J:106650 )

♂ • prostatic adenocarcinomas are seen from 9 months onward

♂ • adenocarcinomas are seen in all lobes, although more often in the dorsolateral and ventral lobes than anterior lobes

♂ • 6 of 17 mutants at 9-16.2 months of age and 9 of 10 mutants at 18.2-19.1 months exhibit adenocarcinomas

♂ • adenocarcinomas show loss of heterozygosity of Pten

♂ • 2 of 31 mutants develop a rare form of mucinous adenocarcinoma

increased prostate intraepithelial neoplasia incidence ( J:106650 )

♂ • males by 6.5 months of age exhibit hyperplasia and focal-low grade PIN lesions in the prostate

♂ • males older than 7.5 months of age exhibit high-grade PINs

increased metastatic potential ( J:106650 )

• metastasis of adenocarcionma into lymph nodes is observed, with 50-60% penetrance

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:106650

Genotype
MGI:4849441

cn41

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten⁺; Tg(Gfap-cre)77.6Mvs/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6NHsd

mortality/aging

premature death ( J:154673 )

• survival is on average 22 weeks

neoplasm

increased classified tumor incidence ( J:154673 )

• mutants develop multiple visible subcutaneous tumors with 100% penetrance, starting from 4 months of age

• majority of tumors are located on the back and sides

increased neurofibroma incidence ( J:154673 )

• each mutant has more than one lesion with features of human neurofibroma and malignant peripheral nerve sheath tumor

increased neurofibrosarcoma incidence ( J:154673 )

• progressive development of malignant peripheral nerve sheath tumors (MPNST) from neurofibroma, with 100% of mutants showing MPNST when followed for 7 months

• Pten loss of heterozygosity in mutants correlates with MPNST transformation from neurofibromas

nervous system

increased neurofibroma incidence ( J:154673 )

• each mutant has more than one lesion with features of human neurofibroma and malignant peripheral nerve sheath tumor

increased neurofibrosarcoma incidence ( J:154673 )

• progressive development of malignant peripheral nerve sheath tumors (MPNST) from neurofibroma, with 100% of mutants showing MPNST when followed for 7 months

• Pten loss of heterozygosity in mutants correlates with MPNST transformation from neurofibromas

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant peripheral nerve sheath tumor		DOID:5940		J:154673
neurofibromatosis 1		DOID:0111253	OMIM:162200	J:154673

Genotype
MGI:5705328

cn42

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten⁺; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

mortality/aging

premature death ( J:184935 )

♂ • lethality around 40 weeks of age

neoplasm

increased prostate gland adenocarcinoma incidence ( J:184935 )

♂ • mice develop focal neoplastic expansions in the prostate by 10 weeks and invasive carcinoma by 20 weeks

increased metastatic potential ( J:184935 )

♂ • mice develop macrometastatic lesions in the lung and liver with 100% penetrance

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:184935 )

♂ • mice develop focal neoplastic expansions in the prostate by 10 weeks and invasive carcinoma by 20 weeks

reproductive system

increased prostate gland adenocarcinoma incidence ( J:184935 )

♂ • mice develop focal neoplastic expansions in the prostate by 10 weeks and invasive carcinoma by 20 weeks

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:184935

Genotype
MGI:5578649

cn43

• Allelic Composition: Pten^tm1Hwu/Pten⁺; Tmprss2^{tm2.1(ETV1)Sho}/Tmprss2^{tm2.1(ETV1)Sho}; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

mortality/aging

premature death ( J:212219 )

♂ • most mice die before 1 year of age

reproductive system

increased prostate gland adenocarcinoma incidence ( J:212219 )

♂ • invasive with metastasis into the prostate stroma and urogenital area

prostate gland cyst ( J:212219 )

♂ • large

neoplasm

increased prostate gland adenocarcinoma incidence ( J:212219 )

♂ • invasive with metastasis into the prostate stroma and urogenital area

endocrine/exocrine glands

increased prostate gland adenocarcinoma incidence ( J:212219 )

♂ • invasive with metastasis into the prostate stroma and urogenital area

prostate gland cyst ( J:212219 )

♂ • large

growth/size/body

prostate gland cyst ( J:212219 )

♂ • large

Genotype
MGI:3813526

cn44

• Allelic Composition: Pten^tm1Hwu/Pten⁺; Tg(KRT14-cre)#Smr/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * SJL/J

mortality/aging

premature death ( J:138927 )

• mice exhibit decreased survival compared to wild type mice

neoplasm

increased mammary gland tumor incidence ( J:138927 )

• 36% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors

• mammary gland tumors exhibit prominent intraluminal and ductal proliferation

• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis

increased mammary adenocarcinoma incidence ( J:138927 )

endocrine/exocrine glands

increased mammary gland tumor incidence ( J:138927 )

• 36% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors

• mammary gland tumors exhibit prominent intraluminal and ductal proliferation

• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis

increased mammary adenocarcinoma incidence ( J:138927 )

integument

increased mammary gland tumor incidence ( J:138927 )

• 36% of mice exhibit thoracic and abdominal/inguinal mammary gland tumors

• mammary gland tumors exhibit prominent intraluminal and ductal proliferation

• mammary gland tumors ranged from fibroadenomas to adenocarcinomas and ductal carcinomas with dense hyaline collagen or dense fibrosis

increased mammary adenocarcinoma incidence ( J:138927 )

Genotype
MGI:5141742

cn45

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Pten^tm1Hwu/Pten⁺; Tg(Upk2-cre)6Xrw/0
• Genetic Background: involves: 129S4/SvJae * FVB/N

integument

increased skin papilloma incidence ( J:174242 )

• 42% of mutants develop skin papillomas

neoplasm

increased skin papilloma incidence ( J:174242 )

• 42% of mutants develop skin papillomas

Genotype
MGI:5050118

cn46

• Allelic Composition: Pten^tm1Ppp/Pten⁺; Rac1^tm1Tyb/Rac1^tm2Tyb; Edil3^{Tg(Sox2-cre)1Amc}/Edil3⁺
• Genetic Background: involves: 129S/Sv * C3H * C57BL/6 * CBA

embryo

abnormal embryo development ( J:173526 )

• embryo morphology is stated to be indistinguishable from that of mutant mice wild-type for Pten

cellular

abnormal apoptosis ( J:173526 )

• cell death is reduced compared to mutant mice wild-type for Pten

Genotype
MGI:5427499

cn47

• Allelic Composition: Pten^tm1Mro/Pten⁺; Tg(Pbsn-cre)4Prb/0
• Genetic Background: involves: C57BL/6 * DBA/2

Prostate cancer progression in Tg(Pbsn-cre)4Prb/0 Gt(ROSA)26Sor^{tm1(CAG-Bmi1,-EGFP)Nki}/Gt(ROSA)26Sor⁺, Tg(Pbsn-cre)4Prb/0 Pten^tm1Mro/Pten⁺, and Tg(Pbsn-cre)4Prb/0 Gt(ROSA)26Sor^{tm1(CAG-Bmi1,-EGFP)Nki}/Gt(ROSA)26Sor⁺ Pten^tm1Mro/Pten⁺ mice

neoplasm

increased prostate intraepithelial neoplasia incidence ( J:184533 )

♂ • in 40% of mice at 9 months

reproductive system

increased prostate intraepithelial neoplasia incidence ( J:184533 )

♂ • in 40% of mice at 9 months

endocrine/exocrine glands

increased prostate intraepithelial neoplasia incidence ( J:184533 )

♂ • in 40% of mice at 9 months

Genotype
MGI:5467729

cx48

• Allelic Composition: Pten^tm1Rps/Pten⁺; Slc6a4^tm1Kpl/Slc6a4⁺
• Genetic Background: B6.129-Slc6a4^tm1Kpl Pten^tm1Rps

behavior/neurological

abnormal social investigation ( J:144937 )

• 8 week old females show a significant decrease in preference for interacting with a stimulus mouse in a social approach assay, with mice spending significantly less time interacting with the stimulus mouse than in wild-type mice or either single heterozygote, indicating impaired social approach behavior in females

• while 8 week old males do not show a change in preference for social interaction for the first trial, upon reexposure to the same social target in trial 2, males do not show attenuation of preference for social investigation between the first and second trials as seen in wild-type mice, indicating impaired social recognition in males

nervous system

increased brain weight ( J:144937 )

reduced sensorimotor gating ( J:144937 )

• deficits in prepulse inhibition of the acoustic startle response indicate impaired sensorimotor gating

decreased prepulse inhibition ( J:144937 )

• mice show deficits in prepulse inhibition of the acoustic startle response to a similar level as single Pten heterozygotes

• however, mice respond to the olfactory-habituation-dishabituation test normally, indicating normal olfactory function

growth/size/body

megacephaly ( J:144937 )

• macrocephaly that is more severe than in either single heterozygote

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autism spectrum disorder		DOID:0060041		J:144937

Genotype
MGI:5306661

cx49

• Allelic Composition: Grhl3^tm1Jane/Grhl3⁺; Pten^tm1Mak/Pten⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv

integument

increased skin papilloma incidence ( J:178952 )

• in DMBA/TPA treated mice

increased skin squamous cell carcinoma incidence ( J:178952 )

• in DMBA/TPA treated mice to a greater extent than in either single heterozygote

neoplasm

increased skin papilloma incidence ( J:178952 )

• in DMBA/TPA treated mice

increased skin squamous cell carcinoma incidence ( J:178952 )

• in DMBA/TPA treated mice to a greater extent than in either single heterozygote

Genotype
MGI:3717274

cx50

• Allelic Composition: Grb2^tm1Paw/Grb2⁺; Pten^tm1Mak/Pten⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

endocrine/exocrine glands

increased adrenal gland tumor incidence ( J:93530 )

mortality/aging

mortality/aging ( J:93530 )

N • the embryonic lethality seen in Pten^tm1Mak heterozygotes is completely rescued

neoplasm

increased tumor incidence ( J:93530 )

• develop the same tumor types at the same frequency as Pten^tm1Mak heterozygotes, including neoplastic lesions in the breast, endometrium, prostate, adrenal gland, and lymphoid organs; tumor stage, grade, and metastatic potential are similar to that in Pten^tm1Mak heterozygotes

increased adrenal gland tumor incidence ( J:93530 )

increased lymphoma incidence ( J:93530 )

increased endometrial carcinoma incidence ( J:93530 )

♀

reproductive system

increased endometrial carcinoma incidence ( J:93530 )

♀

Genotype
MGI:4848133

cx51

• Allelic Composition: Pten^tm1Rps/Pten⁺; Rictor^{Gt(RRR347)Byg}/Rictor⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * BALB/c * C57BL/6

mortality/aging

extended life span ( J:144810 )

• double mutants tend to live longer than single heterozygous Pten mice

endocrine/exocrine glands

prostate gland hyperplasia ( J:144810 )

♂ • prostates exhibit signs of hyperplasia but lesions are less severe than in single heterozygous Pten mice

reproductive system

prostate gland hyperplasia ( J:144810 )

♂ • prostates exhibit signs of hyperplasia but lesions are less severe than in single heterozygous Pten mice

neoplasm

decreased tumor incidence ( J:144810 )

• mutants are protected from prostate cancer development: only 1 of 10 double mutants developed a tumor compared to 5 of 9 single heterozygous Pten mice

Genotype
MGI:5569928

cx52

• Allelic Composition: Nkx3-1^tm1Mms/Nkx3-1⁺; Pten^tm1Rps/Pten⁺
• Genetic Background: involves: 129S1/Sv * 129S1/SvImJ * C57BL/6J

neoplasm

increased prostate gland tumor incidence ( J:75085 )

♂ • early carcinoma lesions are seen in the prostate at 6 months of age

increased prostate intraepithelial neoplasia incidence ( J:75085 )

♂ • at 6 months of age, high-grade prostatic intraepithelial neoplasia/early carcinoma lesions are seen in 36% of prostates, and by 12 months, all mice show lesions

♂ • multifocal lesions in the prostate are comprised of poorly differentiated cells with prominent and multiple nucleoli, an increased nuclear/cytoplasmic ratio, and frequent mitotic figures

♂ • lesions usually fill the affected prostatic ducts and are highly vascularized, show an increase in cytokeratins, an absence of basal epithelium, and a high proliferative index

♂ • lesions show absence of Nkx3-1 protein expression, although mRNA is present and allelic loss of Pten

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:75085 )

♂ • early carcinoma lesions are seen in the prostate at 6 months of age

increased prostate intraepithelial neoplasia incidence ( J:75085 )

♂ • at 6 months of age, high-grade prostatic intraepithelial neoplasia/early carcinoma lesions are seen in 36% of prostates, and by 12 months, all mice show lesions

♂ • multifocal lesions in the prostate are comprised of poorly differentiated cells with prominent and multiple nucleoli, an increased nuclear/cytoplasmic ratio, and frequent mitotic figures

♂ • lesions usually fill the affected prostatic ducts and are highly vascularized, show an increase in cytokeratins, an absence of basal epithelium, and a high proliferative index

♂ • lesions show absence of Nkx3-1 protein expression, although mRNA is present and allelic loss of Pten

reproductive system

increased prostate gland tumor incidence ( J:75085 )

♂ • early carcinoma lesions are seen in the prostate at 6 months of age

increased prostate intraepithelial neoplasia incidence ( J:75085 )

♂ • at 6 months of age, high-grade prostatic intraepithelial neoplasia/early carcinoma lesions are seen in 36% of prostates, and by 12 months, all mice show lesions

♂ • multifocal lesions in the prostate are comprised of poorly differentiated cells with prominent and multiple nucleoli, an increased nuclear/cytoplasmic ratio, and frequent mitotic figures

♂ • lesions usually fill the affected prostatic ducts and are highly vascularized, show an increase in cytokeratins, an absence of basal epithelium, and a high proliferative index

♂ • lesions show absence of Nkx3-1 protein expression, although mRNA is present and allelic loss of Pten

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:75085

Genotype
MGI:5569926

cx53

• Allelic Composition: Nkx3-1^tm1Mms/Nkx3-1^tm1Mms; Pten^tm1Rps/Pten⁺
• Genetic Background: involves: 129S1/Sv * 129S1/SvImJ * C57BL/6J

neoplasm

increased prostate gland tumor incidence ( J:75085 )

♂ • early carcinoma lesions are seen in the prostate at 6 months of age

increased prostate intraepithelial neoplasia incidence ( J:75085 )

♂ • at 6 months of age, high-grade prostatic intraepithelial neoplasia /early carcinoma lesions are seen in 60% of prostates and by 10 months of age, all mice show lesions

♂ • multifocal lesions are comprised of poorly differentiated cells with prominent and multiple nucleoli, an increased nuclear/cytoplasmic ratio, and frequent mitotic figures

♂ • lesions usually fill the affected prostatic ducts and are highly vascularized, show an increase in cytokeratins, an absence of basal epithelium, and a high proliferative index

♂ • lesions show absence of Nkx3-1 protein expression, although mRNA is present and allelic loss of Pten

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:75085 )

♂ • early carcinoma lesions are seen in the prostate at 6 months of age

increased prostate intraepithelial neoplasia incidence ( J:75085 )

♂ • at 6 months of age, high-grade prostatic intraepithelial neoplasia /early carcinoma lesions are seen in 60% of prostates and by 10 months of age, all mice show lesions

♂ • multifocal lesions are comprised of poorly differentiated cells with prominent and multiple nucleoli, an increased nuclear/cytoplasmic ratio, and frequent mitotic figures

♂ • lesions usually fill the affected prostatic ducts and are highly vascularized, show an increase in cytokeratins, an absence of basal epithelium, and a high proliferative index

♂ • lesions show absence of Nkx3-1 protein expression, although mRNA is present and allelic loss of Pten

reproductive system

increased prostate gland tumor incidence ( J:75085 )

♂ • early carcinoma lesions are seen in the prostate at 6 months of age

increased prostate intraepithelial neoplasia incidence ( J:75085 )

♂ • at 6 months of age, high-grade prostatic intraepithelial neoplasia /early carcinoma lesions are seen in 60% of prostates and by 10 months of age, all mice show lesions

♂ • multifocal lesions are comprised of poorly differentiated cells with prominent and multiple nucleoli, an increased nuclear/cytoplasmic ratio, and frequent mitotic figures

♂ • lesions usually fill the affected prostatic ducts and are highly vascularized, show an increase in cytokeratins, an absence of basal epithelium, and a high proliferative index

♂ • lesions show absence of Nkx3-1 protein expression, although mRNA is present and allelic loss of Pten

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:75085

Genotype
MGI:4848146

cx54

• Allelic Composition: Mlst8^tm1Lex/Mlst8⁺; Pten^tm1Rps/Pten⁺
• Genetic Background: involves: 129S1/Sv * 129S5/SvEvBrd * C57BL/6

mortality/aging

extended life span ( J:144810 )

• double mutants live longer than single heterozygous Pten mice

Genotype
MGI:4848141

cx55

• Allelic Composition: Mtor^{Gt(OST92090)Lex}/Mtor⁺; Pten^tm1Rps/Pten⁺
• Genetic Background: involves: 129S1/Sv * 129S5/SvEvBrd * C57BL/6

mortality/aging

extended life span ( J:144810 )

• double mutants live longer than single heterozygous Pten mice

Genotype
MGI:3848161

cx56

• Allelic Composition: Akt1^tm1Nhy/Akt1⁺; Akt2^tm1Rsg/Akt2^tm1Rsg; Pten^tm1Ppp/Pten⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA/1LacJ

homeostasis/metabolism

increased circulating insulin level ( J:149156 )

• following glucose injection, mice exhibit a greater increase in serum insulin levels compared with similarly treated wild-type mice

impaired glucose tolerance ( J:149156 )

• mice exhibit impaired glucose tolerance that is not as severe as in Akt1^tm1Nhy/Akt1^tm1Nhy Akt2^tm1Rsg/Akt2^tm1Rsg mice

• however, mice exhibit normal glucose serum levels under normal conditions

endocrine/exocrine glands

enlarged pancreatic islets ( J:149156 )

• compared to in Akt2^tm1Rsg homozygotes

Genotype
MGI:3848162

cx57

• Allelic Composition: Akt2^tm1Rsg/Akt2^tm1Rsg; Pten^tm1Ppp/Pten⁺
• Genetic Background: involves: 129S1/Sv * C57BL/6 * DBA/1LacJ

homeostasis/metabolism

decreased circulating insulin level ( J:149156 )

• compared to in Akt2^tm1Rsg homozygotes

impaired glucose tolerance ( J:149156 )

• mice exhibit impaired glucose tolerance that is not as severe as in Akt2^tm1Rsg homozygotes

Genotype
MGI:4836243

cx58

• Allelic Composition: Pten^tm1Ppp/Pten⁺; Tg(Pbsn-TAg)15Tvd/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * DBA/2

endocrine/exocrine glands

increased prostate gland tumor incidence ( J:103408 )

♂ • onset of lesions is accelerated compared to single transgenic Tg(Pbsn-TAg)15Tvd mice; by 8 weeks of age, mutant prostates show pronounced cribriform and tufting of epithelial cells that are not seen until 12 weeks of age in single transgenic Tg(Pbsn-TAg)15Tvd mice

increased prostate gland adenocarcinoma incidence ( J:103408 )

♂ • onset of adenocarcinoma is accelerated compared to single transgenic Tg(Pbsn-TAg)15Tvd mice, most likely due to a reduction in apoptosis

♂ • some prostate abnormalities are different than in single transgenic Tg(Pbsn-TAg)15Tvd mice; pale cell carcinomas appear at around 17 weeks of age as do large focal adenocarcinomas with abundant cytoplasm and abnormal glandular growth patterns

♂ • tumors show local microinvasion as well as invasion to distant sites in the urogenital system such as the seminal vesicle

increased prostate intraepithelial neoplasia incidence ( J:103408 )

♂ • onset of mPIN is accelerated compared to single transgenic Tg(Pbsn-TAg)15Tvd mice, most likely due to a reduction in apoptosis

♂ • mPIN lesions increase in severity with age

abnormal prostate gland physiology ( J:103408 )

♂ • epithelial proliferation in the prostate remains similar to single transgenic Tg(Pbsn-TAg)15Tvd mice

♂ • apoptosis in the prostate is reduced compared to single transgenic Tg(Pbsn-TAg)15Tvd mice

reproductive system

increased prostate gland tumor incidence ( J:103408 )

♂ • onset of lesions is accelerated compared to single transgenic Tg(Pbsn-TAg)15Tvd mice; by 8 weeks of age, mutant prostates show pronounced cribriform and tufting of epithelial cells that are not seen until 12 weeks of age in single transgenic Tg(Pbsn-TAg)15Tvd mice

increased prostate gland adenocarcinoma incidence ( J:103408 )

♂ • onset of adenocarcinoma is accelerated compared to single transgenic Tg(Pbsn-TAg)15Tvd mice, most likely due to a reduction in apoptosis

♂ • some prostate abnormalities are different than in single transgenic Tg(Pbsn-TAg)15Tvd mice; pale cell carcinomas appear at around 17 weeks of age as do large focal adenocarcinomas with abundant cytoplasm and abnormal glandular growth patterns

♂ • tumors show local microinvasion as well as invasion to distant sites in the urogenital system such as the seminal vesicle

increased prostate intraepithelial neoplasia incidence ( J:103408 )

♂ • onset of mPIN is accelerated compared to single transgenic Tg(Pbsn-TAg)15Tvd mice, most likely due to a reduction in apoptosis

♂ • mPIN lesions increase in severity with age

abnormal prostate gland physiology ( J:103408 )

♂ • epithelial proliferation in the prostate remains similar to single transgenic Tg(Pbsn-TAg)15Tvd mice

♂ • apoptosis in the prostate is reduced compared to single transgenic Tg(Pbsn-TAg)15Tvd mice

neoplasm

increased prostate gland tumor incidence ( J:103408 )

♂ • onset of lesions is accelerated compared to single transgenic Tg(Pbsn-TAg)15Tvd mice; by 8 weeks of age, mutant prostates show pronounced cribriform and tufting of epithelial cells that are not seen until 12 weeks of age in single transgenic Tg(Pbsn-TAg)15Tvd mice

increased prostate gland adenocarcinoma incidence ( J:103408 )

♂ • onset of adenocarcinoma is accelerated compared to single transgenic Tg(Pbsn-TAg)15Tvd mice, most likely due to a reduction in apoptosis

♂ • some prostate abnormalities are different than in single transgenic Tg(Pbsn-TAg)15Tvd mice; pale cell carcinomas appear at around 17 weeks of age as do large focal adenocarcinomas with abundant cytoplasm and abnormal glandular growth patterns

♂ • tumors show local microinvasion as well as invasion to distant sites in the urogenital system such as the seminal vesicle

increased prostate intraepithelial neoplasia incidence ( J:103408 )

♂ • onset of mPIN is accelerated compared to single transgenic Tg(Pbsn-TAg)15Tvd mice, most likely due to a reduction in apoptosis

♂ • mPIN lesions increase in severity with age

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:103408

Genotype
MGI:5442747

cx59

• Allelic Composition: Pten^tm1Rps/Pten⁺; Tg(Wnt1)1Hev/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * FVB/N * SJL

neoplasm

increased mammary gland ductal carcinoma incidence ( J:67497 )

• 50% of females develop mammary ductal carcinoma by 3.5 months of age, earlier than single Tg(Wnt1)1Hev hemizygotes, and all females show tumors by 5 months of age

• 2 of 22 tumors in males are mammary in origin

increased metastatic potential ( J:67497 )

• mutants occasionally show pulmonary metastasis

increased adenocarcinoma incidence ( J:67497 )

• tumors are adenocarcinomas with cribiform, cystic and focal papillary growth patterns

• 50% of males develop tumors by 5.5 months and all males develop tumors within 10 months

• 50% of females develop tumors by 3.5 months of age and all females have tumors within 5 months of age

• 6 of 22 tumors in males are bilateral or unilateral muzzle tumors of epithelial origin

• 7 or 11 tumors show loss of Pten heterozygosity

• most mutants (38 of 49) develop only one palpable tumor

increased salivary adenocarcinoma incidence ( J:67497 )

♂ • 14 of 22 tumors in males arise in the salivary tissue

increased mammary adenocarcinoma incidence ( J:67497 )

endocrine/exocrine glands

increased salivary adenocarcinoma incidence ( J:67497 )

♂ • 14 of 22 tumors in males arise in the salivary tissue

increased mammary adenocarcinoma incidence ( J:67497 )

increased mammary gland ductal carcinoma incidence ( J:67497 )

• 50% of females develop mammary ductal carcinoma by 3.5 months of age, earlier than single Tg(Wnt1)1Hev hemizygotes, and all females show tumors by 5 months of age

• 2 of 22 tumors in males are mammary in origin

integument

increased mammary adenocarcinoma incidence ( J:67497 )

increased mammary gland ductal carcinoma incidence ( J:67497 )

• 50% of females develop mammary ductal carcinoma by 3.5 months of age, earlier than single Tg(Wnt1)1Hev hemizygotes, and all females show tumors by 5 months of age

• 2 of 22 tumors in males are mammary in origin

digestive/alimentary system

increased salivary adenocarcinoma incidence ( J:67497 )

♂ • 14 of 22 tumors in males arise in the salivary tissue

craniofacial

increased salivary adenocarcinoma incidence ( J:67497 )

♂ • 14 of 22 tumors in males arise in the salivary tissue

growth/size/body

increased salivary adenocarcinoma incidence ( J:67497 )

♂ • 14 of 22 tumors in males arise in the salivary tissue

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
breast cancer		DOID:1612	OMIM:114480	J:67497

Genotype
MGI:5812674

cx60

• Allelic Composition: Pten^tm1.1Mro/Pten⁺; Sdhb^tm1.2Ics/Sdhb⁺
• Genetic Background: involves: 129S2/SvPas * BALB/c * C57BL/6

endocrine/exocrine glands

increased pheochromocytoma incidence ( J:236514 )

• at 10 months of age, 80% of mice develop a pheochromocytoma

neoplasm

increased pheochromocytoma incidence ( J:236514 )

• at 10 months of age, 80% of mice develop a pheochromocytoma

increased metastatic potential ( J:236514 )

• lung micro-metastasis are seen in 73% of mice

Genotype
MGI:5578651

cx61

• Allelic Composition: Del(16Tmprss2-Erg)1Sho/Del(16Tmprss2-Erg)1Sho; Pten^tm1.1Hwu/Pten⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

neoplasm

increased prostate intraepithelial neoplasia incidence ( J:212219 )

♂

endocrine/exocrine glands

increased prostate intraepithelial neoplasia incidence ( J:212219 )

♂

reproductive system

increased prostate intraepithelial neoplasia incidence ( J:212219 )

♂

Genotype
MGI:5578648

cx62

• Allelic Composition: Pten^tm1.1Hwu/Pten⁺; Tmprss2^{tm2.1(ETV1)Sho}/Tmprss2^{tm2.1(ETV1)Sho}
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

neoplasm

increased prostate intraepithelial neoplasia incidence ( J:212219 )

♂

endocrine/exocrine glands

increased prostate intraepithelial neoplasia incidence ( J:212219 )

♂

reproductive system

increased prostate intraepithelial neoplasia incidence ( J:212219 )

♂

Genotype
MGI:5578646

cx63

• Allelic Composition: Pten^tm1.1Hwu/Pten⁺; Tmprss2^{tm1.1(ERG)Sho}/Tmprss2^{tm1.1(ERG)Sho}
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

neoplasm

increased prostate intraepithelial neoplasia incidence ( J:212219 )

♂

reproductive system

increased prostate intraepithelial neoplasia incidence ( J:212219 )

♂

endocrine/exocrine glands

increased prostate intraepithelial neoplasia incidence ( J:212219 )

♂

Genotype
MGI:5008591

cx64

• Allelic Composition: Gt(ROSA)26Sor^{tm1(H1/tetO-RNAi:Pdpk1)Mrl}/Gt(ROSA)26Sor⁺; Pten^tm1.1Hwu/Pten⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6NTac

neoplasm

increased thyroid adenoma incidence ( J:170965 )

• in doxycycline-treated mice

increased lymphoma incidence ( J:170965 )

• at 6 to 7 months of age in doxycycline-treated mice

endocrine/exocrine glands

increased thyroid adenoma incidence ( J:170965 )

• in doxycycline-treated mice

Genotype
MGI:4848144

cx65

• Allelic Composition: Pten^tm1Rps/Pten⁺; Rptor^tm1Lex/Rptor⁺
• Genetic Background: involves: 129S/SvEvBrd * 129S1/Sv * C57BL/6

mortality/aging

mortality/aging ( J:144810 )

N • mutants exhibit a similar lifespan as single heterozygous Pten mice