Phenotypes associated with this allele

• Allele Symbol: Tg(Tyr-cre/ERT2)13Bos
• Allele Name: transgene insertion 13, Marcus Bosenberg
• Allele ID: MGI:3641203
• Summary: 39 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Hsp90b1^tm1Zhli/Hsp90b1^tm1Zhli Tg(Tyr-cre/ERT2)13Bos/0	B6.Cg-Tg(Tyr-cre/ERT2)13Bos Hsp90b1^tm1Zhli	MGI:6220403
cn2	Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Kras^tm4Tyj/Kras^+ Tg(Tyr-cre/ERT2)13Bos/0	B6J.Cg-Tg(Tyr-cre/ERT2)13Bos Cdkn2a^tm2.1Nesh Kras^tm4Tyj	MGI:5752237
cn3	Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Nras^tm1.1Nesh/Nras^tm1.1Nesh Tg(Tyr-cre/ERT2)13Bos/0	B6J.Cg-Tg(Tyr-cre/ERT2)13Bos Nras^tm1.1Nesh Cdkn2a^tm2.1Nesh	MGI:5752235
cn4	Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Nras^tm1.1Nesh/Nras^tm1.1Nesh Stk11^tm1.1Rdp/Stk11^tm1.1Rdp Tg(Tyr-cre/ERT2)13Bos/0	B6J.Cg-Tg(Tyr-cre/ERT2)13Bos Nras^tm1.1Nesh Cdkn2a^tm2.1Nesh Stk11^tm1.1Rdp	MGI:5752239
cn5	Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Nras^tm1Tyj/Nras^tm1Tyj Tg(Tyr-cre/ERT2)13Bos/0	B6J.Cg-Tg(Tyr-cre/ERT2)13Bos Nras^tm1Tyj Cdkn2a^tm2.1Nesh	MGI:5752233
cn6	Gt(ROSA)26Sor^tm1(GNAQ*)Cvrk/Gt(ROSA)26Sor^+ Tg(Tyr-cre/ERT2)13Bos/0	C3FeJ.Cg-Tg(Tyr-cre/ERT2)13Bos Gt(ROSA)26Sor^tm1(GNAQ*)Cvrk/Cvrk	MGI:5702889
cn7	Trp53^tm1Brn/Trp53^tm1Brn Tg(Tyr-cre/ERT2)13Bos/0 Tg(Tyr-NRAS*Q61K)1Bee/0	FVB.Cg-Tg(Tyr-cre/ERT2)13Bos Trp53^tm1Brn Tg(Tyr-NRAS*Q61K)1Bee	MGI:5645995
cn8	Ezh2^tm1.1Nesh/Ezh2^+ Nras^tm1.1Nesh/Nras^+ Tg(Tyr-cre/ERT2)13Bos/0	involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB	MGI:6393932
cn9	Braf^tm1Mmcm/Braf^+ Ezh2^tm1.1Nesh/Ezh2^+ Tg(Tyr-cre/ERT2)13Bos/0	involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB	MGI:6393921
cn10	Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Nras^tm1.1Nesh/Nras^+ Tg(Tyr-cre/ERT2)13Bos/0	involves: 129 * 129S4/SvJae * 129P2/OlaHsd * C57BL/6 * FVB	MGI:6393936
cn11	Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Ezh2^tm1.1Nesh/Ezh2^+ Nras^tm1.1Nesh/Nras^+ Tg(Tyr-cre/ERT2)13Bos/0	involves: 129 * 129S4/SvJae * 129P2/OlaHsd * C57BL/6 * FVB	MGI:6393935
cn12	Braf^tm1Mmcm/Braf^+ Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Tyr-cre/ERT2)13Bos/0	involves: 129P2/OlaHsd * 129S1/Sv * FVB	MGI:5902129
cn13	Braf^tm1Mmcm/Braf^+ Pten^tm2.1Ppp/Pten^+ Tg(Tyr-cre/ERT2)13Bos/0	involves: 129P2/OlaHsd * 129S1/Sv * FVB	MGI:5902136
cn14	Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Trp53^tm1Brn/Trp53^tm1Brn Tg(Tyr-cre/ERT2)13Bos/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB	MGI:4835042
cn15	Cdkn2a^tm2.1Nesh/Cdkn2a^+ Kras^tm4Tyj/Kras^+ Trp53^tm1Brn/Trp53^+ Tg(Tyr-cre/ERT2)13Bos/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB	MGI:4835045
cn16	Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Kras^tm4Tyj/Kras^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(Tyr-cre/ERT2)13Bos/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB	MGI:4835041
cn17	Kras^tm4Tyj/Kras^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(Tyr-cre/ERT2)13Bos/0	involves: 129P2/OlaHsd * 129S4/SvJae * FVB	MGI:4835046
cn18	Braf^tm1Mmcm/Braf^+ Pten^tm1Rdp/Pten^tm1Rdp Tg(Tyr-cre/ERT2)13Bos/0	involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:5902132
cn19	Braf^tm1Mmcm/Braf^+ Tg(Tyr-cre/ERT2)13Bos/0	involves: 129P2/OlaHsd * C57BL/6 * FVB	MGI:6393928
cn20	Sox10^tm7.1(Sox10)Weg/Sox10^+ Tg(Tyr-cre/ERT2)13Bos/0 Tg(Tyr-NRAS*Q61K)1Bee/0	involves: 129P2/OlaHsd * C57BL/6J * DBA/2 * FVB/N	MGI:5515811
cn21	Braf^tm1Mmcm/Braf^tm1Mmcm Tg(Tyr-cre/ERT2)13Bos/0	involves: 129P2/OlaHsd * FVB	MGI:5902126
cn22	Braf^tm1Mmcm/Braf^+ Tg(Tyr-cre/ERT2)13Bos/0	involves: 129P2/OlaHsd * FVB	MGI:5902125
cn23	Ednrb^tm1Nrd/Ednrb^tm1Nrd Gt(ROSA)26Sor^tm14(CAG-tdTomato)Hze/Gt(ROSA)26Sor^+ Tg(Tyr-cre/ERT2)13Bos/0	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6J	MGI:6269398
cn24	Ednrb^tm1Nrd/Ednrb^tm1Nrd Tg(Dct-lacZ)#Ove/0 Tg(Tyr-cre/ERT2)13Bos/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N	MGI:6269406
cn25	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Tyr-cre/ERT2)13Bos/0	involves: 129S1/Sv * FVB	MGI:5902133
cn26	Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Kras^tm4Tyj/Kras^+ Tg(Tyr-cre/ERT2)13Bos/0	involves: 129S4/SvJae * C57BL/6 * FVB	MGI:4835044
cn27	Kras^tm4Tyj/Kras^+ Tg(Tyr-cre/ERT2)13Bos/0	involves: 129S4/SvJae * FVB	MGI:4835047
cn28	Pten^tm1Rdp/Pten^tm1Rdp Tg(Tyr-cre/ERT2)13Bos/0	involves: 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:5902135
cn29	Mc1r^tm1.1Mymi/Mc1r^tm1.1Mymi Tg(Tyr-cre/ERT2)13Bos/0	involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NTac	MGI:6269418
cn30	Mc1r^tm1.1Mymi/Mc1r^tm1.1Mymi Tg(KRT14-rtTA)F42Efu/0 Tg(tetO-EDN1,-lacZ)9Mhus/0 Tg(Tyr-cre/ERT2)13Bos/0	involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NTac * FVB	MGI:6269451
cn31	Mc1r^tm1.1Mymi/Mc1r^tm1.1Mymi Tg(Dct-lacZ)#Ove/0 Tg(Tyr-cre/ERT2)13Bos/0	involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NTac * FVB/N	MGI:6269447
cn32	Braf^tm1Tuv/Braf^tm1Tuv Gt(ROSA)26Sor^tm1(sb13)Tuv/Gt(ROSA)26Sor^+ Tg(Tyr-cre/ERT2)13Bos/0 TgTn(sb-T2/Onc)#Dla/0	involves: 129S6/SvEvTac * FVB/N	MGI:5318067
cn33	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Pten^tm1Rps/Pten^tm1Rps Tg(Tyr-cre/ERT2)13Bos/0	involves: 129/Sv * 129S1/Sv * C57BL/6J * FVB/N * SJL	MGI:4418448
cn34	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Ctnnb1^tm1Mmt/Ctnnb1^tm1Mmt Pten^tm1Rps/Pten^tm1Rps Tg(Tyr-cre/ERT2)13Bos/0	involves: 129/Sv * C57BL/6J * FVB * SJL	MGI:4418449
cn35	Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Gt(ROSA)26Sor^tm1(rtTA,EGFP)Nagy/Gt(ROSA)26Sor^+ Pten^tm1Rdp/Pten^tm1Rdp Tg(tetO-BRAF*V600E)29Lc/0 Tg(Tyr-cre/ERT2)13Bos/0	involves: 129/Sv * C57BL/6J * FVB * SJL	MGI:5700641
cn36	Pikfyve^tm2.1Tssk/Pikfyve^tm2.1Tssk Tg(Tyr-cre/ERT2)13Bos/0	involves: C57BL/6 * C57BL/6J	MGI:6256964
cn37	Gt(ROSA)26Sor^tm4(ACTB-tdTomato,-EGFP)Luo/Gt(ROSA)26Sor^+ Pikfyve^tm2.1Tssk/Pikfyve^tm2.1Tssk Tg(Tyr-cre/ERT2)13Bos/0	involves: C57BL/6 * C57BL/6J	MGI:6256968
cn38	Ctnnb1^tm2Kem/Ctnnb1^tm2Kem Tg(KRT14-rtTA)F42Efu/0 Tg(tetO-EDN1,-lacZ)9Mhus/0 Tg(Tyr-cre/ERT2)13Bos/0	involves: C57BL/6J * FVB	MGI:6269417
cn39	Gt(ROSA)26Sor^tm1(GNAQ*)Cvrk/Gt(ROSA)26Sor^tm1Sor Tg(Tyr-cre/ERT2)13Bos/0	STOCK Tg(Tyr-cre/ERT2)13Bos Gt(ROSA)26Sor^tm1(GNAQ*)Cvrk/Gt(ROSA)26Sor^tm1Sor/Cvrk	MGI:6792069

Genotype
MGI:6220403

cn1

• Allelic Composition: Hsp90b1^tm1Zhli/Hsp90b1^tm1Zhli; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: B6.Cg-Tg(Tyr-cre/ERT2)13Bos Hsp90b1^tm1Zhli

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

pigmentation

abnormal hair follicle melanogenesis ( J:265851 )

• mice show decreased levels of melanin in hair bulbs in the 4-OHT-treated area relative to control mice

reduced hair shaft melanin granule number ( J:265851 )

• mice show decreased levels of melanin in hair shafts plucked from the 4-OHT-treated area relative to control mice

diluted coat color ( J:265851 )

• following 4 weeks of topical application of 4-hydroxytamoxifen (4-OHT) to shaved skin on the right flank, coat hair that re-grows in the 4-OHT-treated area is grey/white in color, whereas hair re-grown in the vehicle (ethanol)-treated left flank is black; control mice treated with either 4-OHT or vehicle show no change in hair color

integument

abnormal hair follicle melanogenesis ( J:265851 )

• mice show decreased levels of melanin in hair bulbs in the 4-OHT-treated area relative to control mice

reduced hair shaft melanin granule number ( J:265851 )

• mice show decreased levels of melanin in hair shafts plucked from the 4-OHT-treated area relative to control mice

diluted coat color ( J:265851 )

• following 4 weeks of topical application of 4-hydroxytamoxifen (4-OHT) to shaved skin on the right flank, coat hair that re-grows in the 4-OHT-treated area is grey/white in color, whereas hair re-grown in the vehicle (ethanol)-treated left flank is black; control mice treated with either 4-OHT or vehicle show no change in hair color

Genotype
MGI:5752237

cn2

• Allelic Composition: Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh; Kras^tm4Tyj/Kras⁺; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: B6J.Cg-Tg(Tyr-cre/ERT2)13Bos Cdkn2a^tm2.1Nesh Kras^tm4Tyj

pigmentation

hyperpigmentation ( J:220627 )

• mice treated with 4-hydroxytamoxifen (4-OHT) neonatally exhibit the presence of nevi and hyperpigmented regions on the paws and tails

integument

increased cutaneous melanoma incidence ( J:220627 )

• mice treated with 4-OHT neonatally develop melanoma with 76% penetrance and a median latency of 36.3 weeks

• melanomas contain both spindle-cell and desmoplastic cell types with no overt signs of macrometastatic spread

neoplasm

increased cutaneous melanoma incidence ( J:220627 )

• mice treated with 4-OHT neonatally develop melanoma with 76% penetrance and a median latency of 36.3 weeks

• melanomas contain both spindle-cell and desmoplastic cell types with no overt signs of macrometastatic spread

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
skin melanoma		DOID:8923	OMIM:608035 OMIM:612263	J:220627

Genotype
MGI:5752235

cn3

• Allelic Composition: Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh; Nras^tm1.1Nesh/Nras^tm1.1Nesh; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: B6J.Cg-Tg(Tyr-cre/ERT2)13Bos Nras^tm1.1Nesh Cdkn2a^tm2.1Nesh

cellular

abnormal melanocyte proliferation ( J:220627 )

• melanocytes treated with 4-hydroxytamoxifen (4-OHT) to induce cre activity exhibit decreased proliferation in culture and cease to proliferate after 2-3 passages

integument

increased cutaneous melanoma incidence ( J:220627 )

• mice treated with 4-OHT neonatally readily develop melanoma with 70% penetrance and a median latency of 26.3 weeks

• melanomas contain both spindle-cell and desmoplastic cell types with no overt signs of macrometastatic spread

pigmentation

abnormal melanocyte proliferation ( J:220627 )

• melanocytes treated with 4-hydroxytamoxifen (4-OHT) to induce cre activity exhibit decreased proliferation in culture and cease to proliferate after 2-3 passages

hyperpigmentation ( J:220627 )

• mice treated with 4-OHT neonatally exhibit the presence of nevi and hyperpigmented regions on the paws and tails

neoplasm

increased cutaneous melanoma incidence ( J:220627 )

• mice treated with 4-OHT neonatally readily develop melanoma with 70% penetrance and a median latency of 26.3 weeks

• melanomas contain both spindle-cell and desmoplastic cell types with no overt signs of macrometastatic spread

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
skin melanoma		DOID:8923	OMIM:608035 OMIM:612263	J:220627

Genotype
MGI:5752239

cn4

• Allelic Composition: Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh; Nras^tm1.1Nesh/Nras^tm1.1Nesh; Stk11^tm1.1Rdp/Stk11^tm1.1Rdp; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: B6J.Cg-Tg(Tyr-cre/ERT2)13Bos Nras^tm1.1Nesh Cdkn2a^tm2.1Nesh Stk11^tm1.1Rdp

integument

increased cutaneous melanoma incidence ( J:220627 )

• mice treated with 4-hydroxytamoxifen (4-OHT) neonatally or in adulthood exhibit enhanced nevus formation

• mice treated with 4-OHT neonatally develop melanoma with 85% penetrance and a median latency of 22.1 weeks

neoplasm

increased cutaneous melanoma incidence ( J:220627 )

• mice treated with 4-hydroxytamoxifen (4-OHT) neonatally or in adulthood exhibit enhanced nevus formation

• mice treated with 4-OHT neonatally develop melanoma with 85% penetrance and a median latency of 22.1 weeks

increased metastatic potential ( J:220627 )

• 36% of mice treated with 4-OHT neonatally that develop melanoma show macrometastatic spread to lymph nodes, lung, spleen and/or liver

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
skin melanoma		DOID:8923	OMIM:608035 OMIM:612263	J:220627

Genotype
MGI:5752233

cn5

• Allelic Composition: Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh; Nras^tm1Tyj/Nras^tm1Tyj; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: B6J.Cg-Tg(Tyr-cre/ERT2)13Bos Nras^tm1Tyj Cdkn2a^tm2.1Nesh

cellular

abnormal melanocyte proliferation ( J:220627 )

• melanocytes treated with 4-hydroxytamoxifen (4-OHT) to induce cre activity exhibit decreased proliferation in culture and cease to proliferate after 2-3 passages

integument

increased cutaneous melanoma incidence ( J:220627 )

• melanoma is very rare in mice treated with 4-OHT neonatally, with 1 in 29 mice developing tumors when observed for 80 weeks

pigmentation

abnormal melanocyte proliferation ( J:220627 )

• melanocytes treated with 4-hydroxytamoxifen (4-OHT) to induce cre activity exhibit decreased proliferation in culture and cease to proliferate after 2-3 passages

hyperpigmentation ( J:220627 )

• mice treated with 4-OHT neonatally exhibit the presence of nevi and hyperpigmented regions on the paws and tails

neoplasm

increased cutaneous melanoma incidence ( J:220627 )

• melanoma is very rare in mice treated with 4-OHT neonatally, with 1 in 29 mice developing tumors when observed for 80 weeks

Genotype
MGI:5702889

cn6

• Allelic Composition: Gt(ROSA)26Sor^{tm1(GNAQ*)Cvrk}/Gt(ROSA)26Sor⁺; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: C3FeJ.Cg-Tg(Tyr-cre/ERT2)13Bos Gt(ROSA)26Sor^{tm1(GNAQ*)Cvrk}/Cvrk

pigmentation

abnormal melanocyte morphology ( J:225597 )

• melanocytic hyperplasia in tamoxifen treated mice after 2 and 6.5 months

hyperpigmentation ( J:225597 )

• 2 months after tamoxifen treatment

vision/eye

exophthalmos ( J:225597 )

• 2 months after tamoxifen treatment

behavior/neurological

behavior/neurological phenotype ( J:225597 )

N • tamoxifen-treated mice do not exhibit any behavioral abnormalities

neoplasm

neoplasm ( J:225597 )

N • tamoxifen-treated mice fail to develop uveal melanoma

Genotype
MGI:5645995

cn7

• Allelic Composition: Trp53^tm1Brn/Trp53^tm1Brn; Tg(Tyr-cre/ERT2)13Bos/0; Tg(Tyr-NRAS*Q61K)1Bee/0
• Genetic Background: FVB.Cg-Tg(Tyr-cre/ERT2)13Bos Trp53^tm1Brn Tg(Tyr-NRAS*Q61K)1Bee

neoplasm

increased cutaneous melanoma incidence ( J:222847 )

• spontaneous development of malignant melanoma by 200 days of age in all mice treated with tamoxifen

• tumors of tamoxifen-treated mice are relatively small, with regular ovoid shape and high levels of Ki-67 staining

• naevi are not seen above dermal malignant melanomas in tamoxifen treated mice, although small nests of melanocytes in a subepidermal location are occasionally seen

• early lesions of tamoxifen treated mice do not show evidence of tumor derivation from the upper dermis and appear to be derived from follicular or other deep dermal precursors

• majority of tumors of tamoxifen treated mice are located on the back

increased incidence of tumors by UV-induction ( J:222847 )

• all mice treated with tamoxifen develop malignant melanoma before 150 days of age after a single neonatal UVB dose

• tamoxifen-treated mice show a diminished response of melanocyte emigration from the upper regions of hair follicles to the epidermal basal layer 3-5 days after neonatal UV radiation compared to controls

integument

increased cutaneous melanoma incidence ( J:222847 )

• spontaneous development of malignant melanoma by 200 days of age in all mice treated with tamoxifen

• tumors of tamoxifen-treated mice are relatively small, with regular ovoid shape and high levels of Ki-67 staining

• naevi are not seen above dermal malignant melanomas in tamoxifen treated mice, although small nests of melanocytes in a subepidermal location are occasionally seen

• early lesions of tamoxifen treated mice do not show evidence of tumor derivation from the upper dermis and appear to be derived from follicular or other deep dermal precursors

• majority of tumors of tamoxifen treated mice are located on the back

Genotype
MGI:6393932

cn8

• Allelic Composition: Ezh2^tm1.1Nesh/Ezh2⁺; Nras^tm1.1Nesh/Nras⁺; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB

neoplasm

neoplasm ( J:239472 )

N • tamoxifen-treated mice do not show acceleration of melanomagenesis and do not form melanoma compared to single Nras conditional mutants

Genotype
MGI:6393921

cn9

• Allelic Composition: Braf^tm1Mmcm/Braf⁺; Ezh2^tm1.1Nesh/Ezh2⁺; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129 * 129P2/OlaHsd * C57BL/6 * FVB

neoplasm

increased melanoma incidence ( J:239472 )

• tamoxifen-treated mice show accelerated tumorigenesis of unpigmented, nonmetastatic melanoma compared to single Braf conditional mutants

Genotype
MGI:6393936

cn10

• Allelic Composition: Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh; Nras^tm1.1Nesh/Nras⁺; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129 * 129S4/SvJae * 129P2/OlaHsd * C57BL/6 * FVB

neoplasm

increased melanoma incidence ( J:239472 )

• tamoxifen-treated mice develop melanoma

Genotype
MGI:6393935

cn11

• Allelic Composition: Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh; Ezh2^tm1.1Nesh/Ezh2⁺; Nras^tm1.1Nesh/Nras⁺; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129 * 129S4/SvJae * 129P2/OlaHsd * C57BL/6 * FVB

neoplasm

increased melanoma incidence ( J:239472 )

• tamoxifen-treated mice develop melanoma similarly to conditional Nras and Cdkn2a double mutants

Genotype
MGI:5902129

cn12

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

integument

increased cutaneous melanoma incidence ( J:151023 )

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

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

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

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

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

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

neoplasm

increased cutaneous melanoma incidence ( J:151023 )

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

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

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

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

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

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

increased metastatic potential ( J:151023 )

• spread of melanoma in 4-HT treated mice is seen into the regional draining lymph nodes in 100% of mice and to the lungs in some cases

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

Genotype
MGI:5902136

cn13

• 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:4835042

cn14

• Allelic Composition: Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB

neoplasm

increased melanoma incidence ( J:164588 )

• 1 in 19 (5%) mice treated with tamoxifen neonatally develop melanomas with spindle-like morphology at a median latency of greater than 52 weeks

pigmentation

abnormal melanocyte morphology ( J:164588 )

• tamoxifen-treated mice exhibit melanocytic proliferation unlike wild-type mice

hyperpigmentation ( J:164588 )

• tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice

Genotype
MGI:4835045

cn15

• Allelic Composition: Cdkn2a^tm2.1Nesh/Cdkn2a⁺; Kras^tm4Tyj/Kras⁺; Trp53^tm1Brn/Trp53⁺; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB

neoplasm

increased spindle cell carcinoma incidence ( J:164588 )

• tamoxifen-treated mice develop melanomas with spindle-like morphology

increased melanoma incidence ( J:164588 )

• 3 of 7 (43%) mice treated with tamoxifen neonatally develop melanomas with spindle-like morphology at a median latency greater than 52 weeks compared with Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Kras^tm4Tyj/Kras⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(Tyr-cre/ERT2)13Bos mice whose median latency is 14 weeks

pigmentation

abnormal melanocyte morphology ( J:164588 )

• tamoxifen-treated mice exhibit melanocytic proliferation unlike wild-type mice

hyperpigmentation ( J:164588 )

• tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice

Genotype
MGI:4835041

cn16

• Allelic Composition: Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh; Kras^tm4Tyj/Kras⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB

mortality/aging

premature death ( J:164588 )

• all mice treated with tamoxifen neonatally die within 14 weeks of treatment due to aggressive melanomas with spindle-like morphology unlike control mice in which only one mouse develops melanoma over a period of 60 weeks

neoplasm

increased tumor growth/size ( J:164588 )

• tumor growth is more aggressive than in Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp Tg(Tyr-HRAS)60Lc mice

increased spindle cell carcinoma incidence ( J:164588 )

• tamoxifen-treated mice develop melanomas with spindle-like morphology

increased melanoma incidence ( J:164588 )

• all mice treated with tamoxifen neonatally die within 14 weeks of treatment due to aggressive melanomas with spindle-like morphology unlike control mice in which only one mouse develops melanoma over a period of 60 weeks

• tumors in tamoxifen-treated mice occur on the flank, ear, and tail

• the number of tumors in tamoxifen-treated mice is greater than in similarly treated Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Kras^tm4Tyj/Kras⁺ Tg(Tyr-cre/ERT2)13Bos mice or Kras^tm4Tyj/Kras⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(Tyr-cre/ERT2)13Bos mice

• by 15 weeks, 17 of 27 adult mice treated with tamoxifen develop melanomas at the site of application and depilation

• however, no uveal tumors are observed

pigmentation

abnormal melanocyte morphology ( J:164588 )

• tamoxifen-treated mice exhibit melanocytic proliferation unlike wild-type mice

hyperpigmentation ( J:164588 )

• tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice

Genotype
MGI:4835046

cn17

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * FVB

neoplasm

increased spindle cell carcinoma incidence ( J:164588 )

• tamoxifen-treated mice develop melanomas with spindle-like morphology

increased melanoma incidence ( J:164588 )

• 5 of 11 mice treated with tamoxifen neonatally develop melanomas with spindle-like morphology at a longer latency (median latency 31 weeks) than in Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Kras^tm4Tyj/Kras⁺ Trp53^tm1Brn/Trp53^tm1BrnTg(Tyr-cre/ERT2)13Bos mice (median latency 14 weeks)

pigmentation

abnormal melanocyte morphology ( J:164588 )

• tamoxifen-treated mice exhibit melanocytic proliferation unlike wild-type mice

hyperpigmentation ( J:164588 )

• tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice

Genotype
MGI:5902132

cn18

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

integument

increased cutaneous melanoma incidence ( J:151023 )

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

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

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

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

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

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

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

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

neoplasm

increased cutaneous melanoma incidence ( J:151023 )

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

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

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

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

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

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

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

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

increased metastatic potential ( J:151023 )

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

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

Genotype
MGI:6393928

cn19

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

neoplasm

neoplasm ( J:239472 )

N • tamoxifen-treated mice do not develop melanoma

Genotype
MGI:5515811

cn20

• Allelic Composition: Sox10^{tm7.1(Sox10)Weg}/Sox10⁺; Tg(Tyr-cre/ERT2)13Bos/0; Tg(Tyr-NRAS*Q61K)1Bee/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * DBA/2 * FVB/N

pigmentation

pigmentation phenotype ( J:193443 )

N • mice injected with tamoxifen at 2 months of age do not exhibit hyperpigmentation in the back skin, snout and paws at 12 months of age, indicating reversion of lesions that are seen in single Tg(Tyr-NRAS*Q61K)1Bee mutants

Genotype
MGI:5902126

cn21

• Allelic Composition: Braf^tm1Mmcm/Braf^tm1Mmcm; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129P2/OlaHsd * FVB

pigmentation

abnormal melanocyte morphology ( J:151023 )

• topical administration of 4-hydroxytamoxifen (4-HT) to the ear, tail or flank results in the development of benign melanocytic hyperplasias that are larger and more highly pigmented than in conditional heterozygotes

Genotype
MGI:5902125

cn22

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

pigmentation

abnormal melanocyte morphology ( J:151023 )

• pigmented lesions in 4-HT treated mice are frequently located at the dermal-epidermal junction with extension into the dermis, indicating melanocytic nevi

• other melanocytic proliferations form in the dermis with no junctional component in 4-HT treated mice

integument

skin lesions ( J:151023 )

• mice treated with 4-hydroxytamoxifen (4-HT) either topically or systemically develop highly pigmented lesions that are detected by 21-28 days after 4-HT administration; these are small papular pigmented lesions that are not malignant

• topical administration of high concentrations of 4-HT occasionally results in periocular lesions on the face and on the glabrous skin of the paws

Genotype
MGI:6269398

cn23

• Allelic Composition: Ednrb^tm1Nrd/Ednrb^tm1Nrd; Gt(ROSA)26Sor^{tm14(CAG-tdTomato)Hze}/Gt(ROSA)26Sor⁺; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6J

integument

abnormal coat/hair pigmentation ( J:231435 )

• following induction of Cre-mediated recombination by TAM treatment at 3 weeks of age (1st telogen), mice show a noticeable hair-graying phenotype by the 2nd telogen; hair graying persists through the next hair cycle (3rd telogen), unlike in control mice

abnormal hair follicle melanocyte morphology ( J:231435 )

• following TAM treatment at 3 weeks of age (1st telogen), mice exhibit unpigmented hair follicles that contain fewer differentiated melanocytes in the bulb by anagen IV

absent hair follicle melanin granules ( J:231435 )

• following TAM treatment at 3 weeks of age (1st telogen), mice exhibit unpigmented hair follicles unlike control mice

reduced hair shaft melanin granule number ( J:231435 )

• following TAM treatment at 3 weeks of age (1st telogen), >65% of hair shafts lack melanin, leading to a hair-graying phenotype at the 2nd and 3rd telogen

pigmentation

abnormal melanocyte proliferation ( J:231435 )

• following TAM treatment at 3 weeks of age (1st telogen), melanocyte stem cells (McSCs) in unpigmented hair follicles show less BrdU incorporation than those in pigmented hair follicles of control mice at anagen III

abnormal coat/hair pigmentation ( J:231435 )

• following induction of Cre-mediated recombination by TAM treatment at 3 weeks of age (1st telogen), mice show a noticeable hair-graying phenotype by the 2nd telogen; hair graying persists through the next hair cycle (3rd telogen), unlike in control mice

abnormal hair follicle melanocyte morphology ( J:231435 )

• following TAM treatment at 3 weeks of age (1st telogen), mice exhibit unpigmented hair follicles that contain fewer differentiated melanocytes in the bulb by anagen IV

absent hair follicle melanin granules ( J:231435 )

• following TAM treatment at 3 weeks of age (1st telogen), mice exhibit unpigmented hair follicles unlike control mice

reduced hair shaft melanin granule number ( J:231435 )

• following TAM treatment at 3 weeks of age (1st telogen), >65% of hair shafts lack melanin, leading to a hair-graying phenotype at the 2nd and 3rd telogen

decreased melanocyte number ( J:231435 )

• following TAM treatment at 3 weeks of age (1st telogen), unpigmented hair follicles contain fewer differentiated melanocytes in the bulb by anagen IV, as shown by a decreased number of tomato+ melanocytes expressing differentiation markers Dct, MITF, and S100

• % of apoptotic (Casp3+) bulb melanocytes is significantly increased relative to that in control mice at anagen VI

cellular

abnormal melanocyte proliferation ( J:231435 )

• following TAM treatment at 3 weeks of age (1st telogen), melanocyte stem cells (McSCs) in unpigmented hair follicles show less BrdU incorporation than those in pigmented hair follicles of control mice at anagen III

Genotype
MGI:6269406

cn24

• Allelic Composition: Ednrb^tm1Nrd/Ednrb^tm1Nrd; Tg(Dct-lacZ)#Ove/0; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * FVB/N

pigmentation

abnormal epidermal melanocyte morphology ( J:231435 )

• following TAM treatment immediately after wounding at 8 weeks of age, mice show a significantly reduced number of epidermal melanocytes in the wound area both at day 0 and day 8 after re- epithelialization relative to control mice

• however, no signs of apoptosis are observed, suggesting normal survival of epidermal melanocytes after wounding

decreased melanocyte number ( J:231435 )

• following initial TAM treatment during 2nd anagen, the number of Dct-LacZ+ melanocyte stem cells (McSCs) in unpigmented hair follicles is significantly lower than that in control mice by the 2nd telogen; most unpigmented hair follicles completely lack McSCs by the 3rd and 4th telogen

integument

abnormal epidermal melanocyte morphology ( J:231435 )

• following TAM treatment immediately after wounding at 8 weeks of age, mice show a significantly reduced number of epidermal melanocytes in the wound area both at day 0 and day 8 after re- epithelialization relative to control mice

• however, no signs of apoptosis are observed, suggesting normal survival of epidermal melanocytes after wounding

Genotype
MGI:5902133

cn25

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

pigmentation

pigmentation phenotype ( J:151023 )

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

Genotype
MGI:4835044

cn26

• Allelic Composition: Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh; Kras^tm4Tyj/Kras⁺; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * FVB

neoplasm

increased spindle cell carcinoma incidence ( J:164588 )

• tamoxifen-treated mice develop melanomas with spindle-like morphology

increased melanoma incidence ( J:164588 )

• 8 of 11 (73%) mice treated with tamoxifen neonatally develop melanomas with spindle-like morphology formation at a longer latency (median latency 24 weeks) than in Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Kras^tm4Tyj/Kras⁺ Trp53^tm1Brn/Trp53^tm1Brn Tg(Tyr-cre/ERT2)13Bos mice (median latency 14 weeks)

pigmentation

abnormal melanocyte morphology ( J:164588 )

• tamoxifen-treated mice exhibit melanocyte proliferation unlike wild-type mice

hyperpigmentation ( J:164588 )

• tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice

Genotype
MGI:4835047

cn27

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129S4/SvJae * FVB

neoplasm

increased melanoma incidence ( J:164588 )

• 1 in 14 tamoxifen treated mice develops melanoma with a median tumor latency greater than 52 weeks

pigmentation

abnormal melanocyte morphology ( J:164588 )

• tamoxifen-treated mice exhibit melanocytic proliferation unlike wild-type mice

hyperpigmentation ( J:164588 )

• tamoxifen-treated mice develop pigmented macules in the paws and tail unlike wild-type mice

Genotype
MGI:5902135

cn28

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

pigmentation

pigmentation phenotype ( J:151023 )

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

Genotype
MGI:6269418

cn29

• Allelic Composition: Mc1r^tm1.1Mymi/Mc1r^tm1.1Mymi; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NTac

pigmentation

yellow coat color ( J:231435 )

• following TAM treatment, mice exhibit a yellow coat color at 2nd telogen, similar to mice homozygous for the Mc1r^e allele

integument

yellow coat color ( J:231435 )

• following TAM treatment, mice exhibit a yellow coat color at 2nd telogen, similar to mice homozygous for the Mc1r^e allele

Genotype
MGI:6269451

cn30

• Allelic Composition: Mc1r^tm1.1Mymi/Mc1r^tm1.1Mymi; Tg(KRT14-rtTA)F42Efu/0; Tg(tetO-EDN1,-lacZ)9Mhus/0; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NTac * FVB

pigmentation

abnormal epidermal melanocyte morphology ( J:231435 )

• following wounding, mice show a significant increase of epidermal melanocytes containing dark pigment in the wound site, indicating that Edn1 overexpression in epithelial cells can rescue the defect of epidermal melanocyte regeneration caused by MC1R loss in the melanocyte lineage

integument

abnormal epidermal melanocyte morphology ( J:231435 )

• following wounding, mice show a significant increase of epidermal melanocytes containing dark pigment in the wound site, indicating that Edn1 overexpression in epithelial cells can rescue the defect of epidermal melanocyte regeneration caused by MC1R loss in the melanocyte lineage

Genotype
MGI:6269447

cn31

• Allelic Composition: Mc1r^tm1.1Mymi/Mc1r^tm1.1Mymi; Tg(Dct-lacZ)#Ove/0; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * C57BL/6NTac * FVB/N

pigmentation

abnormal epidermal melanocyte morphology ( J:231435 )

• following wounding, mice show a significant reduction of epidermal melanocytes in the wound site relative to control mice

integument

abnormal epidermal melanocyte morphology ( J:231435 )

• following wounding, mice show a significant reduction of epidermal melanocytes in the wound site relative to control mice

Genotype
MGI:5318067

cn32

• Allelic Composition: Braf^tm1Tuv/Braf^tm1Tuv; Gt(ROSA)26Sor^tm1(sb13)Tuv/Gt(ROSA)26Sor⁺; Tg(Tyr-cre/ERT2)13Bos/0; TgTn(sb-T2/Onc)#Dla/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

neoplasm

increased melanoma incidence ( J:177503 )

• in tamoxifen-treated mice

Genotype
MGI:4418448

cn33

• Allelic Composition: Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp; Pten^tm1Rps/Pten^tm1Rps; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129/Sv * 129S1/Sv * C57BL/6J * FVB/N * SJL

neoplasm

increased melanoma incidence ( J:155731 )

• following 4-hydroxytamoxifen (4-OHT) application, all mice develop melanoma over a 9 month period unlike wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
melanoma		DOID:1909		J:155731

Genotype
MGI:4418449

cn34

• Allelic Composition: Cdkn2a^tm1Rdp/Cdkn2a^tm1Rdp; Ctnnb1^tm1Mmt/Ctnnb1^tm1Mmt; Pten^tm1Rps/Pten^tm1Rps; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: 129/Sv * C57BL/6J * FVB * SJL

neoplasm

increased melanoma incidence ( J:155731 )

• following 4-hydroxytamoxifen (4-OHT) application, all mice develop melanoma over a 9 month period unlike wild-type mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
melanoma		DOID:1909		J:155731

Genotype
MGI:5700641

cn35

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

neoplasm

increased melanoma incidence ( J:221902 )

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

• withdrawal of doxycycline leads to rapid tumor regression

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

Genotype
MGI:6256964

cn36

• Allelic Composition: Pikfyve^tm2.1Tssk/Pikfyve^tm2.1Tssk; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: C57BL/6 * C57BL/6J

Hair greying in tamoxifen-treated Pikfyve^tm2.1Tssk/Pikfyve^tm2.1Tssk Tg(Tyr-cre/ERT2)13Bos/0 mice

pigmentation

abnormal coat/hair pigmentation ( J:262141 )

• after tamoxifen (4-OHT) treatment for 21 days (P28-P50) followed by shave depilation at P50 to induce the 3rd hair cycle, both pigmented and unpigmented hairs are noted at P60, whereas control mice fed a normal diet show fully pigmented hair growth

abnormal hair follicle melanocyte morphology ( J:262141 )

• after 4-OHT treatment (P28-P50) followed by shave depilation at P50, some, but not all, anagen hair follicles (HFs) show a vacuolated phenotype, indicating that Cre-mediated deletion is not 100% efficient; some HFs show normal melanocyte morphology ("normal"), some HFs exhibit accumulation of cells with intracellular vesicles with some residual pigment ("intermediate"), while others show accumulation of cells with intracellular vesicles with little to no pigment ("abnormal")

• EM of skin biopsies taken at P60 show anagen hair bulbs containing melanocytes in various conditions: ~40% appear normal, another ~40% show severe vacuolization exhibiting vesicles within vacuoles resembling multivesicular bodies with very few if any melanosomes, and ~20% show an intermediate phenotype with fewer melanosomes generally of earlier stages

reduced hair shaft melanin granule number ( J:262141 )

• dorsal hairs from 4-OHT-treated mice accumulate ~50% less melanin relative to hairs from control mice at P85, P105, and P365

diluted coat color ( J:262141 )

• after 4-OHT treatment for 29 days (P21-P50) followed by shave depilation of a dorsal region at P50, mice exhibit hair greying with white hairs first seen in the depilated area at P85

• when mice are switched off tamoxifen and fed a normal chow starting at P50, more white hairs are visually apparent at P105

• numerous white hairs accumulate on the head and upper back (areas that have never been shave depilated) by P365, indicating that greying is accelerated but not induced by depilation

• greying is not progressive as mice continue to maintain the same relative level of depigmentation over the course of a year

abnormal endosome to melanosome transport ( J:262141 )

• after DOPA incubation, some of the multivesicular endosome-like structures observed in epidermal melanocytes of 4-OHT-treated mice contain DOPA reaction product, suggesting that TYR may be trapped within this compartment

abnormal melanosome maturation ( J:262141 )

• after 4-OHT treatment, primary melanocytes isolated from newborn mice show a significantly reduced number of pigmented melanosomes per cell relative to vehicle-treated melanocytes

• 4-OHT-treated primary melanocytes exhibit accumulation of full length premelanosome protein (PMEL) relative to vehicle-treated melanocytes

• in culture, some 4-OHT-treated melanocytes accumulate single membrane structures resembling multivesicular endosomes with few stage IV melanosomes, while others accumulate early and late stage melanosomes with a few single membrane structures

integument

abnormal coat/hair pigmentation ( J:262141 )

• after tamoxifen (4-OHT) treatment for 21 days (P28-P50) followed by shave depilation at P50 to induce the 3rd hair cycle, both pigmented and unpigmented hairs are noted at P60, whereas control mice fed a normal diet show fully pigmented hair growth

abnormal hair follicle melanocyte morphology ( J:262141 )

• after 4-OHT treatment (P28-P50) followed by shave depilation at P50, some, but not all, anagen hair follicles (HFs) show a vacuolated phenotype, indicating that Cre-mediated deletion is not 100% efficient; some HFs show normal melanocyte morphology ("normal"), some HFs exhibit accumulation of cells with intracellular vesicles with some residual pigment ("intermediate"), while others show accumulation of cells with intracellular vesicles with little to no pigment ("abnormal")

• EM of skin biopsies taken at P60 show anagen hair bulbs containing melanocytes in various conditions: ~40% appear normal, another ~40% show severe vacuolization exhibiting vesicles within vacuoles resembling multivesicular bodies with very few if any melanosomes, and ~20% show an intermediate phenotype with fewer melanosomes generally of earlier stages

reduced hair shaft melanin granule number ( J:262141 )

• dorsal hairs from 4-OHT-treated mice accumulate ~50% less melanin relative to hairs from control mice at P85, P105, and P365

diluted coat color ( J:262141 )

• after 4-OHT treatment for 29 days (P21-P50) followed by shave depilation of a dorsal region at P50, mice exhibit hair greying with white hairs first seen in the depilated area at P85

• when mice are switched off tamoxifen and fed a normal chow starting at P50, more white hairs are visually apparent at P105

• numerous white hairs accumulate on the head and upper back (areas that have never been shave depilated) by P365, indicating that greying is accelerated but not induced by depilation

• greying is not progressive as mice continue to maintain the same relative level of depigmentation over the course of a year

Genotype
MGI:6256968

cn37

• Allelic Composition: Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/Gt(ROSA)26Sor⁺; Pikfyve^tm2.1Tssk/Pikfyve^tm2.1Tssk; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: C57BL/6 * C57BL/6J

Early greying in Pikfyve^tm2.1Tssk/Pikfyve^tm2.1Tssk Tg(Tyr-cre/ERT2)13Bos/0 Gt(ROSA)26Sor^{tm4(ACTB-tdTomato,-EGFP)Luo}/Gt(ROSA)26Sor⁺ mice

pigmentation

diluted coat color ( J:262141 )

• after 4-OHT treatment (P21-P50) mice exhibit an early greying phenotype at P50

• however, GFP+ cells associated with hair follicles are present at P100, indicating that melanocyte survival is not significantly affected

integument

diluted coat color ( J:262141 )

• after 4-OHT treatment (P21-P50) mice exhibit an early greying phenotype at P50

• however, GFP+ cells associated with hair follicles are present at P100, indicating that melanocyte survival is not significantly affected

Genotype
MGI:6269417

cn38

• Allelic Composition: Ctnnb1^tm2Kem/Ctnnb1^tm2Kem; Tg(KRT14-rtTA)F42Efu/0; Tg(tetO-EDN1,-lacZ)9Mhus/0; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: involves: C57BL/6J * FVB

pigmentation

abnormal melanocyte differentiation ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, McSCs fail to differentiate as shown by the absence of pigment and Tyr expression in McSCs at anagen onset

abnormal melanocyte proliferation ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, McSCs fail to proliferate as shown by the absence of Ki67 expression in McSCs at anagen onset; this is in contrast to control littermates that overexpress Edn1 with intact Wnt signaling

abnormal coat/hair pigmentation ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, mice develop a hair-graying phenotype by the 2nd telogen; this is in contrast to control littermates that overexpress Edn1 with intact Wnt signaling

abnormal epidermal melanocyte morphology ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, wounded mice show a significant reduction in the number of epidermal melanocytes relative to control littermates that overexpress Edn1 with intact Wnt signaling

integument

abnormal coat/hair pigmentation ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, mice develop a hair-graying phenotype by the 2nd telogen; this is in contrast to control littermates that overexpress Edn1 with intact Wnt signaling

abnormal epidermal melanocyte morphology ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, wounded mice show a significant reduction in the number of epidermal melanocytes relative to control littermates that overexpress Edn1 with intact Wnt signaling

cellular

abnormal melanocyte differentiation ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, McSCs fail to differentiate as shown by the absence of pigment and Tyr expression in McSCs at anagen onset

abnormal melanocyte proliferation ( J:231435 )

• following depletion of beta-catenin in McSCs during anagen, McSCs fail to proliferate as shown by the absence of Ki67 expression in McSCs at anagen onset; this is in contrast to control littermates that overexpress Edn1 with intact Wnt signaling

Genotype
MGI:6792069

cn39

• Allelic Composition: Gt(ROSA)26Sor^{tm1(GNAQ*)Cvrk}/Gt(ROSA)26Sor^tm1Sor; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: STOCK Tg(Tyr-cre/ERT2)13Bos Gt(ROSA)26Sor^{tm1(GNAQ*)Cvrk}/Gt(ROSA)26Sor^tm1Sor/Cvrk

limbs/digits/tail

decreased tail pigmentation ( J:312561 )

integument

reduced hair shaft melanin granule number ( J:312561 )

• in inter-follicular epidermis of tamoxifen-treated mice

abnormal epidermal pigmentation ( J:312561 )

decreased tail pigmentation ( J:312561 )

decreased skin pigmentation ( J:312561 )

pigmentation

reduced hair shaft melanin granule number ( J:312561 )

• in inter-follicular epidermis of tamoxifen-treated mice

abnormal epidermal pigmentation ( J:312561 )

decreased tail pigmentation ( J:312561 )

decreased skin pigmentation ( J:312561 )

decreased melanocyte number ( J:312561 )

• in inter-follicular epidermis of tamoxifen-treated mice