Phenotypes associated with this allele

• Allele Symbol: Tg(TPO-cre)1Shk
• Allele Name: transgene insertion 1, Shioko Kimura
• Allele ID: MGI:3653644
• Summary: 25 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Kras^tm4Tyj/Kras^+ Tg(TPO-cre)1Shk/0	129.Cg-Kras^tm4Tyj Tg(Tpo-cre)1Shk	MGI:5897670
cn2	Kras^tm4Tyj/Kras^+ Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0	129.Cg-Kras^tm4Tyj Tg(Tpo-cre)1Shk Pten^tm2.1Ppp	MGI:5897668
cn3	Pten^tm2.1Ppp/Pten^tm2.1Ppp Trp53^tm1Brn/Trp53^tm1Brn Tg(TPO-cre)1Shk/0	129.Cg-Tg(TPO-cre)1Shk Trp53^tm1Brn Pten^tm2.1Ppp	MGI:5897837
cn4	Cdkn1b^tm1Ako/Cdkn1b^+ Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0	129S1.Cg-Cdkn1b^tm1Ako Tg(TPO-cre)1Shk Pten^tm2.1Ppp	MGI:4838319
cn5	Cdkn1b^tm1Ako/Cdkn1b^tm1Ako Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0	129S1.Cg-Cdkn1b^tm1Ako Tg(TPO-cre)1Shk Pten^tm2.1Ppp	MGI:4838318
cn6	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0	129S1.Cg-Pten^tm2.1Ppp Tg(TPO-cre)1Shk	MGI:4838317
cn7	Pten^tm1.1Mwst/Pten^tm1.1Mwst Tg(TPO-cre)1Shk/0	involves: 129 * FVB/NCr	MGI:5897778
cn8	Braf^tm1Cpri/Braf^tm1Cpri Tshr^tm1Rmar/Tshr^tm1Rmar Tg(TPO-cre)1Shk/0	involves: 129P2/OlaHsd * 129S1/Sv * FVB/NCr	MGI:5779645
cn9	Hras^tm1Jaf/Hras^tm1Jaf Trp53^tm1Brn/Trp53^tm1Brn Tg(TPO-cre)1Shk/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6 * FVB/NCr	MGI:5784771
cn10	Hras^tm1Jaf/Hras^tm1Jaf Nf2^tm2Gth/Nf2^tm2Gth Tg(TPO-cre)1Shk/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6 * FVB/NCr	MGI:5784770
cn11	Braf^tm1Cpri/Braf^tm1Cpri Gnas^tm3Lsw/Gnas^tm3Lsw Tg(TPO-cre)1Shk/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * FVB/NCr	MGI:5779648
cn12	Nf2^tm2Gth/Nf2^tm2Gth Tg(TPO-cre)1Shk/0	involves: 129P2/OlaHsd * FVB/NCr	MGI:5784767
cn13	Braf^tm1Cpri/Braf^tm1Cpri Tg(TPO-cre)1Shk/0	involves: 129P2/OlaHsd * FVB/NCr	MGI:5779643
cn14	Braf^tm1Mmcm/? Tg(TPO-cre)1Shk/0	involves: 129P2/OlaHsd * FVB/NCr	MGI:5780076
cn15	Hras^tm1Jaf/Hras^tm1Jaf Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(TPO-cre)1Shk/0	involves: 129S1/Sv * 129S6/SvEvTac * FVB/NCr	MGI:5784778
cn16	Prkar1a^tm1.2Lsk/Prkar1a^tm1.2Lsk Tg(TPO-cre)1Shk/0	involves: 129S1/Sv * 129X1/SvJ * FVB/NCr	MGI:5897776
cn17	Prkar1a^tm1.2Lsk/Prkar1a^tm1.2Lsk Pten^tm1.1Mwst/Pten^tm1.1Mwst Tg(TPO-cre)1Shk/0	involves: 129S1/Sv * 129X1/SvJ * FVB/NCr	MGI:5897675
cn18	Prkar1a^tm1.2Lsk/Prkar1a^+ Pten^tm1.1Mwst/Pten^+ Tg(TPO-cre)1Shk/0	involves: 129S1/Sv * 129X1/SvJ * FVB/NCr	MGI:5897775
cn19	Pten^tm1Hwu/Pten^tm1Hwu Tg(TPO-cre)1Shk/0	involves: 129S4/SvJae * FVB/NCr	MGI:5294347
cn20	Pten^tm1Hwu/Pten^tm1Hwu Tg(CAG-EGFP,-PAX8/PPARG)1Rkoe/0 Tg(TPO-cre)1Shk/0	involves: 129S4/SvJae * FVB/NCr * FVB/NJ	MGI:5294346
cn21	Hras^tm1Jaf/? Tg(TPO-cre)1Shk/0	involves: 129S6/SvEvTac * FVB/NCr	MGI:5779651
cn22	Gnas^tm3Lsw/Gnas^tm3Lsw Tg(TPO-cre)1Shk/0	involves: 129S6/SvEvTac * FVB/NCr	MGI:5779650
cn23	Hras^tm1Jaf/Hras^tm1Jaf Tg(TPO-cre)1Shk/0	involves: 129S6/SvEvTac * FVB/NCr	MGI:5784765
cn24	Nkx2-1^tm2Shk/Nkx2-1^tm2Shk Tg(TPO-cre)1Shk/0	involves: 129X1/SvJ * FVB/NCr	MGI:3653705
cn25	Tg(CAG-EGFP,-PAX8/PPARG)1Rkoe/0 Tg(TPO-cre)1Shk/0	involves: FVB/NCr * FVB/NJ	MGI:5294345

Genotype
MGI:5897670

cn1

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Tg(TPO-cre)1Shk/0
• Genetic Background: 129.Cg-Kras^tm4Tyj Tg(Tpo-cre)1Shk

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

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:147732 )

N • mice are indistinguishable from wild-type mice and show no alterations of the thyroid gland

Genotype
MGI:5897668

cn2

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

mortality/aging

premature death ( J:147732 )

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

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

endocrine/exocrine glands

enlarged thyroid gland ( J:147732 )

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

increased thyroid carcinoma incidence ( J:147732 )

• mice rapidly develop thyroid follicular carcinomas

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

homeostasis/metabolism

increased thyroxine level ( J:147732 )

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

neoplasm

increased thyroid carcinoma incidence ( J:147732 )

• mice rapidly develop thyroid follicular carcinomas

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

increased metastatic potential ( J:147732 )

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

Genotype
MGI:5897837

cn3

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

mortality/aging

premature death ( J:211100 )

• median survival is 38.4 weeks

neoplasm

increased thyroid carcinoma incidence ( J:211100 )

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

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

increased metastatic potential ( J:211100 )

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

endocrine/exocrine glands

enlarged thyroid gland ( J:211100 )

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

increased thyroid carcinoma incidence ( J:211100 )

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

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

homeostasis/metabolism

decreased thyroid-stimulating hormone level ( J:211100 )

• reduction in TSH serum levels

• however, T4 levels are normal

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

Genotype
MGI:4838319

cn4

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

mortality/aging

premature death ( J:165293 )

• mean survival is 58 weeks of age

neoplasm

increased thyroid adenoma incidence ( J:165293 )

• no gender differences in development of adenomas

increased thyroid carcinoma incidence ( J:165293 )

• no gender differences in development of carcinomas

endocrine/exocrine glands

increased thyroid adenoma incidence ( J:165293 )

• no gender differences in development of adenomas

increased thyroid carcinoma incidence ( J:165293 )

• no gender differences in development of carcinomas

Genotype
MGI:4838318

cn5

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

mortality/aging

premature death ( J:165293 )

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

endocrine/exocrine glands

thyroid gland hyperplasia ( J:165293 )

respiratory system

respiratory distress ( J:165293 )

• hyperplastic thyroids cause dyspnea and prevent feeding

Genotype
MGI:4838317

cn6

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

mortality/aging

premature death ( J:165293 )

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

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

endocrine/exocrine glands

thyroid gland hyperplasia ( J:165293 )

• enlarged thyroid

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

increased thyroid adenoma incidence ( J:165293 )

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

increased thyroid carcinoma incidence ( J:165293 )

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

homeostasis/metabolism

increased thyroxine level ( J:165293 )

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

decreased thyroid-stimulating hormone level ( J:165293 )

• aging mice exhibit suppression of thyroid-stimulating hormone

neoplasm

increased thyroid adenoma incidence ( J:165293 )

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

increased thyroid carcinoma incidence ( J:165293 )

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

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

Genotype
MGI:5897778

cn7

• Allelic Composition: Pten^tm1.1Mwst/Pten^tm1.1Mwst; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129 * FVB/NCr

endocrine/exocrine glands

abnormal thyroid follicular cell morphology ( J:225245 )

• mice exhibit benign follicular thyroid hyperplasia

Genotype
MGI:5779645

cn8

• Allelic Composition: Braf^tm1Cpri/Braf^tm1Cpri; Tshr^tm1Rmar/Tshr^tm1Rmar; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * FVB/NCr

endocrine/exocrine glands

abnormal thyroid follicle morphology ( J:168249 )

• architecture of thyroid follicles is disrupted at 3 weeks of age

increased thyroid tumor incidence ( J:168249 )

• mice develop low-grade papillary thyroid cancer by 9 weeks of age, however, tumors are smaller and lack the characteristic tall cell features and are less invasive than in single Braf^tm1Cpri conditional mice

small thyroid gland ( J:168249 )

neoplasm

increased thyroid tumor incidence ( J:168249 )

• mice develop low-grade papillary thyroid cancer by 9 weeks of age, however, tumors are smaller and lack the characteristic tall cell features and are less invasive than in single Braf^tm1Cpri conditional mice

Genotype
MGI:5784771

cn9

• Allelic Composition: Hras^tm1Jaf/Hras^tm1Jaf; Trp53^tm1Brn/Trp53^tm1Brn; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6 * FVB/NCr

endocrine/exocrine glands

increased thyroid tumor incidence ( J:231492 )

• mice develop poorly differentiated thyroid cancer

neoplasm

increased thyroid tumor incidence ( J:231492 )

• mice develop poorly differentiated thyroid cancer

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

Genotype
MGI:5784770

cn10

• Allelic Composition: Hras^tm1Jaf/Hras^tm1Jaf; Nf2^tm2Gth/Nf2^tm2Gth; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * Black Swiss * C57BL/6 * FVB/NCr

endocrine/exocrine glands

increased thyroid tumor incidence ( J:231492 )

• mice develop large thyroid cancers with high penetrance, with most being poorly differentiated thyroid cancer

• treatment with AZD6244 results in a reduction of tumor size

neoplasm

increased thyroid tumor incidence ( J:231492 )

• mice develop large thyroid cancers with high penetrance, with most being poorly differentiated thyroid cancer

• treatment with AZD6244 results in a reduction of tumor size

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

Genotype
MGI:5779648

cn11

• Allelic Composition: Braf^tm1Cpri/Braf^tm1Cpri; Gnas^tm3Lsw/Gnas^tm3Lsw; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129P2/OlaHsd * 129S6/SvEvTac * FVB/NCr

endocrine/exocrine glands

increased thyroid tumor incidence ( J:168249 )

• mice develop smaller papillary thyroid tumors with greatly attenuated histological features resembling indolent papillary thyroid cancer in humans compared to single Braf^tm1Cpri conditional mutants

neoplasm

increased thyroid tumor incidence ( J:168249 )

• mice develop smaller papillary thyroid tumors with greatly attenuated histological features resembling indolent papillary thyroid cancer in humans compared to single Braf^tm1Cpri conditional mutants

Genotype
MGI:5784767

cn12

• Allelic Composition: Nf2^tm2Gth/Nf2^tm2Gth; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/NCr

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:231492 )

• about 65% of mice exhibit mild nodular hyperplasia after 18 months

neoplasm

neoplasm ( J:231492 )

N • mice do not develop thyroid cancer

Genotype
MGI:5779643

cn13

• Allelic Composition: Braf^tm1Cpri/Braf^tm1Cpri; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/NCr

growth/size/body

decreased body weight ( J:168249 )

• mice weigh about 50% less than wild-type littermates by weaning

homeostasis/metabolism

increased circulating thyroxine level ( J:168249 )

• by 5 weeks of age, serum T4 levels are decreased

increased circulating thyroid-stimulating hormone level ( J:168249 )

• by 5 weeks of age, serum TSH levels are about 500-fold greater than in wild-type mice

neoplasm

increased thyroid tumor incidence ( J:168249 )

• mice develop infiltrative papillary thyroid cancer with complete penetrance by 5 weeks of age

• tumors encompass the entire thyroid gland and have features of aggressive human papillary thyroid cancer with papillae lined by tall cells, with increased number of mitoses, nuclear clearing, and pseudonuclear inclusions

• administration of levothyroxine (L-T4) soon after birth for 3 weeks does not prevent the onset or alter the characteristics of papillary thyroid tumors

• administration of L-T4 for 3 weeks beginning at 5 weeks of age when all mice have tumors does not decrease the mitotic rate or alter the severity of the tumors

• mice treated with the MEK1/2 inhibitor PD325901 for 3 weeks beginning at 3 weeks of age exhibit a decrease in thyroid tumor volume and a modest reduction in proliferative index of tumors

increased thyroid carcinoma incidence ( J:168249 )

• tumor cells frequently invade perithyroidal tissues

• 66% of tumors invade into surrounding skeletal muscle by 5 weeks and vascular invasion is common

endocrine/exocrine glands

increased thyroid tumor incidence ( J:168249 )

• mice develop infiltrative papillary thyroid cancer with complete penetrance by 5 weeks of age

• tumors encompass the entire thyroid gland and have features of aggressive human papillary thyroid cancer with papillae lined by tall cells, with increased number of mitoses, nuclear clearing, and pseudonuclear inclusions

• administration of levothyroxine (L-T4) soon after birth for 3 weeks does not prevent the onset or alter the characteristics of papillary thyroid tumors

• administration of L-T4 for 3 weeks beginning at 5 weeks of age when all mice have tumors does not decrease the mitotic rate or alter the severity of the tumors

• mice treated with the MEK1/2 inhibitor PD325901 for 3 weeks beginning at 3 weeks of age exhibit a decrease in thyroid tumor volume and a modest reduction in proliferative index of tumors

increased thyroid carcinoma incidence ( J:168249 )

• tumor cells frequently invade perithyroidal tissues

• 66% of tumors invade into surrounding skeletal muscle by 5 weeks and vascular invasion is common

decreased activity of thyroid gland ( J:168249 )

• mice are euthyroid at P3, however by 5 weeks of age, mice are hypothyroid

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
papillary thyroid carcinoma		DOID:3969	OMIM:188550	J:168249

Genotype
MGI:5780076

cn14

• Allelic Composition: Braf^tm1Mmcm/?; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129P2/OlaHsd * FVB/NCr

growth/size/body

decreased birth weight ( J:172205 )

• mice exhibit low birth weight and fail to thrive

Genotype
MGI:5784778

cn15

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

endocrine/exocrine glands

increased thyroid tumor incidence ( J:231492 )

• mice develop poorly differentiated thyroid cancer

neoplasm

increased thyroid tumor incidence ( J:231492 )

• mice develop poorly differentiated thyroid cancer

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

Genotype
MGI:5897776

cn16

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

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:241066 )

• thyroids show increased cellularity but retain a follicular pattern of growth

enlarged thyroid gland ( J:241066 )

• 100% of mice exhibit enlargement of the thyroid

increased thyroid carcinoma incidence ( J:225245 , J:241066 )

• thyroids exhibit locally invasive follicular thyroid carcinoma (J:225245)

• tumors exhibit high proliferation rate (J:225245)

• mice develop follicular thyroid carcinoma at a rate of 43% by one year of age (J:241066)

• tumors exhibit increased proliferation compared to wild-type thyroid glands (J:241066)

• however, none of the tumors show widely invasive or angio-invasive behavior (J:241066)

increased activity of thyroid gland ( J:241066 )

• mice are hyperthyroid

homeostasis/metabolism

increased thyroxine level ( J:241066 )

• T4 levels are elevated, indicating hyperthyroidism

decreased thyroid-stimulating hormone level ( J:241066 )

• TSH levels are lower but not statistically significant due to wide variation in wild-type mice

neoplasm

increased thyroid carcinoma incidence ( J:225245 , J:241066 )

• thyroids exhibit locally invasive follicular thyroid carcinoma (J:225245)

• tumors exhibit high proliferation rate (J:225245)

• mice develop follicular thyroid carcinoma at a rate of 43% by one year of age (J:241066)

• tumors exhibit increased proliferation compared to wild-type thyroid glands (J:241066)

• however, none of the tumors show widely invasive or angio-invasive behavior (J:241066)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
follicular thyroid carcinoma		DOID:3962	OMIM:188470	J:241066

Genotype
MGI:5897675

cn17

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

mortality/aging

premature death ( J:225245 )

• median survival age of 6 months

growth/size/body

weight loss ( J:225245 )

♂ • males exhibit lower body weight beginning at 1 month of age which becomes statistically significant at 5 months of age

endocrine/exocrine glands

enlarged thyroid gland ( J:225245 )

increased thyroid carcinoma incidence ( J:225245 )

• 100% of mice develop follicular thyroid carcinoma by 8 weeks of age, showing capsular and/or vascular invasion

• tumors show a molecular signature similar to human sporadic follicular thyroid cancer

increased activity of thyroid gland ( J:225245 )

• mice are hyperthyroid

adipose tissue

decreased subcutaneous adipose tissue amount ( J:225245 )

• reduction in subcutaneous adipose tissue

decreased abdominal adipose tissue amount ( J:225245 )

• reduction in visceral adipose tissue

homeostasis/metabolism

increased circulating thyroxine level ( J:225245 )

• free T4 levels are increased

integument

decreased subcutaneous adipose tissue amount ( J:225245 )

• reduction in subcutaneous adipose tissue

neoplasm

increased thyroid carcinoma incidence ( J:225245 )

• 100% of mice develop follicular thyroid carcinoma by 8 weeks of age, showing capsular and/or vascular invasion

• tumors show a molecular signature similar to human sporadic follicular thyroid cancer

increased metastatic potential ( J:225245 )

• metastatic follicular thyroid carcinoma is seen in the lungs of 27% of mice; metastases are well differentiated, maintain follicular structure with colloid, and stain for thyroglobulin

• tumors exhibit only mild increases in proliferation rate compared to those in single homozygous Prkar1a^tm1.2Lsk Tg(TPO-cre)1Shk/0 mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
follicular thyroid carcinoma		DOID:3962	OMIM:188470	J:241066

Genotype
MGI:5897775

cn18

• 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:5294347

cn19

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129S4/SvJae * FVB/NCr

endocrine/exocrine glands

enlarged thyroid gland ( J:177181 )

• enlarged in a smooth and symmetrical manner with abundant colloid

Genotype
MGI:5294346

cn20

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(CAG-EGFP,-PAX8/PPARG)1Rkoe/0; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129S4/SvJae * FVB/NCr * FVB/NJ

endocrine/exocrine glands

abnormal thyroid gland morphology ( J:177181 )

• pioglitazone-fed mice exhibit lipid accumulation in thyroid cells

enlarged thyroid gland ( J:177181 )

• 100-fold increase in size

• larger than in Pten^tm1Hwu/Pten^tm1Hwu Tg(TPO-cre)1Shk mice

• irregularly shaped, mutlinodular, more cellular than colloid

• however, pioglitazone (a PPARG inhibitor) decreases thyroid size

increased thyroid carcinoma incidence ( J:177181 )

• with metastasis to the lungs and soft tissues

• however, pioglitazone (a PPARG inhibitor) induces a lipogenic antitumor response

abnormal thymus physiology ( J:177181 )

• pioglitazone-fed mice exhibit decreased thyroid size due to increased apoptosis

homeostasis/metabolism

increased circulating thyroxine level ( J:177181 )

• 6-fold

• however, pioglitazone normalizes thyroid function

increased circulating triiodothyronine level ( J:177181 )

• 3.5-fold

• however, pioglitazone normalizes thyroid function

neoplasm

increased thyroid carcinoma incidence ( J:177181 )

• with metastasis to the lungs and soft tissues

• however, pioglitazone (a PPARG inhibitor) induces a lipogenic antitumor response

immune system

abnormal thymus physiology ( J:177181 )

• pioglitazone-fed mice exhibit decreased thyroid size due to increased apoptosis

hematopoietic system

abnormal thymus physiology ( J:177181 )

• pioglitazone-fed mice exhibit decreased thyroid size due to increased apoptosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thyroid gland carcinoma		DOID:3963		J:177181

Genotype
MGI:5779651

cn21

• Allelic Composition: Hras^tm1Jaf/?; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/NCr

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:168249 )

N • mice exhibit normal serum thyroid-stimulating hormone (TSH) and thyroxine (T4) levels

neoplasm

neoplasm ( J:168249 )

N • mice treated with the goitrogen 6-propyl-2-thiouracil (PTU) for up to 20 weeks of age develop benign goiters and increases in TSH but do not develop thyroid cancer

Genotype
MGI:5779650

cn22

• Allelic Composition: Gnas^tm3Lsw/Gnas^tm3Lsw; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/NCr

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:168249 )

N • mice exhibit normal thyroid histology

Genotype
MGI:5784765

cn23

• Allelic Composition: Hras^tm1Jaf/Hras^tm1Jaf; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/NCr

neoplasm

neoplasm ( J:231492 )

N • mice do not develop thyroid cancer

Genotype
MGI:3653705

cn24

• Allelic Composition: Nkx2-1^tm2Shk/Nkx2-1^tm2Shk; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: 129X1/SvJ * FVB/NCr

endocrine/exocrine glands

abnormal thyroid follicle morphology ( J:111027 )

• glands consist mostly of atrophic or degenerative follicles, and multiple smaller follicles lined by cuboidal to columnar epithelial cells in various ratios; atrophic/degenerative follicles had various sizes and shapes and are lined with flattened to cuboidal epithelial cells

• colloid in the lumen of cells in these follicles is partially or almost completely depleted

• most of these cells have lost Titf1 expression

• space between normal and atrophic/degenerative follicles is filled with small follicles resembling hyperplastic thyroid follicles containing little or no colloid in their lumens

• cultured follicular cells form irregular-shaped polygonal structures lacking colloid accumulation compared to mature, spherical colloid-containing follicles formed by cells from Titf1^tm2Shk homozygotes

small thyroid gland ( J:111027 )

• mice expressing highly elevated TSH levels have the most severely affected throid glands; size of thyroid glands is reduced to about half the diameter of control thyroid glands

homeostasis/metabolism

increased circulating thyroid-stimulating hormone level ( J:111027 )

• mean serum TSH levels are higher than in Titf1^tm1Shk/ Titf1^tm2Shk mice or Titf1^tm2Shk homozygous mice but statistical significance was not obtained

• extremely high TSH serum levels are sporadically observed

neoplasm

increased adenoma incidence ( J:111027 )

• small follicles between normal and atrophic/degenerative follicles occasionally form nodular lesions considered to be follicular adenoma

Genotype
MGI:5294345

cn25

• Allelic Composition: Tg(CAG-EGFP,-PAX8/PPARG)1Rkoe/0; Tg(TPO-cre)1Shk/0
• Genetic Background: involves: FVB/NCr * FVB/NJ

endocrine/exocrine glands

thyroid gland hyperplasia ( J:177181 )

• by 6 months (benign)

neoplasm

neoplasm ( J:177181 )

N • mice do not develop abnormal tumors