Phenotypes associated with this allele

• Allele Symbol: Tg(Th-MYCN)41Waw
• Allele Name: transgene insertion 41, William A Weiss
• Allele ID: MGI:3039395
• Summary: 14 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Tg(CAG-Alk*F1174L,-luc)60Jhsc/0 Tg(Dbh-icre)1Gsc/0 Tg(Th-MYCN)41Waw/0	involves: 129X1/SvJ * BALB/c * C57BL/6 * C57BL/6J * FVB/N	MGI:6196047
cn2	Alk^tm1.1(ALK*F1174L)Heno/Alk^tm1.1(ALK*F1174L)Heno Tg(Mpz-cre)94Imeg/0 Tg(Th-MYCN)41Waw/0	involves: 129X1/SvJ * BALB/c * C57BL/6 * SJL	MGI:6476981
cn3	Alk^tm1.1(ALK*F1174L)Heno/Alk^+ Tg(Mpz-cre)94Imeg/0 Tg(Th-MYCN)41Waw/0	involves: 129X1/SvJ * BALB/c * C57BL/6 * SJL	MGI:6476983
cx4	Ret^tm2.1Cos/? Tg(Th-MYCN)41Waw/0	involves: 129S1/Sv * BALB/c * C57BL/6J	MGI:6196323
cx5	Alk^tm2.1Ics/? Tg(Th-MYCN)41Waw/0	involves: 129S2/SvPas * 129X1/SvJ * BALB/c * C57BL/6 * C57BL/6J	MGI:5789376
cx6	Alk^tm1.1Ics/? Tg(Th-MYCN)41Waw/0	involves: 129S2/SvPas * 129X1/SvJ * BALB/c * C57BL/6 * C57BL/6J	MGI:5789375
cx7	Nf1^tm1Tyj/Nf1^+ Tg(Th-MYCN)41Waw/0	involves: 129S2/SvPas * BALB/c * C57BL/6J	MGI:5009552
cx8	Rb1^tm1Tyj/Rb1^+ Tg(Th-MYCN)41Waw/0	involves: 129S2/SvPas * BALB/c * C57BL/6J	MGI:5009553
cx9	Tg(Th-MYCN)41Waw/0 Trp53^tm1Brd/Trp53^+	involves: 129S7/SvEvBrd * BALB/c * C57BL/6J * FVB/N	MGI:5009554
cx10	Tg(Th-ALK*F1174L)2Loch/0 Tg(Th-MYCN)41Waw/0	involves: 129X1/SvJ * BALB/c * C57BL/6J * CBA	MGI:5636486
tg11	Tg(Th-MYCN)41Waw/Tg(Th-MYCN)41Waw	involves: BALB/c * C57BL/6J	MGI:5009550
tg12	Tg(Th-MYCN)41Waw/0	involves: 129X1/SvJ * BALB/c * C57BL/6J	MGI:5009555
tg13	Tg(Th-MYCN)41Waw/0	involves: BALB/c * C57BL/6J	MGI:5009549
tg14	Tg(Th-MYCN)41Waw/0	involves: BALB/c * C57BL/6J * FVB/N	MGI:5009551

Genotype
MGI:6196047

cn1

• Allelic Composition: Tg(CAG-Alk*F1174L,-luc)60Jhsc/0; Tg(Dbh-icre)1Gsc/0; Tg(Th-MYCN)41Waw/0
• Genetic Background: involves: 129X1/SvJ * BALB/c * C57BL/6 * C57BL/6J * FVB/N

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

neoplasm

increased neuroblastoma incidence ( J:186696 )

• all mice develop neuroblastomas within 48 days of age

• tumor incidence is higher and time to tumor formation is shorter than in mice expressing only Tg(Th-MYCN)41Waw

• tumors show a reduction in the number of genomic aberrations compared to tumors in mice expressing only Tg(Th-MYCN)41Waw or Tg(CAG-Alk*F1174L,-luc)60Jhsc

• mice bearing tumors treated with TAE-684, an ALK inhibitor, show some regression of tumors

nervous system

increased neuroblastoma incidence ( J:186696 )

• all mice develop neuroblastomas within 48 days of age

• tumor incidence is higher and time to tumor formation is shorter than in mice expressing only Tg(Th-MYCN)41Waw

• tumors show a reduction in the number of genomic aberrations compared to tumors in mice expressing only Tg(Th-MYCN)41Waw or Tg(CAG-Alk*F1174L,-luc)60Jhsc

• mice bearing tumors treated with TAE-684, an ALK inhibitor, show some regression of tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:186696

Genotype
MGI:6476981

cn2

• Allelic Composition: Alk^{tm1.1(ALK*F1174L)Heno}/Alk^{tm1.1(ALK*F1174L)Heno}; Tg(Mpz-cre)94Imeg/0; Tg(Th-MYCN)41Waw/0
• Genetic Background: involves: 129X1/SvJ * BALB/c * C57BL/6 * SJL

mortality/aging

premature death ( J:294092 )

• mice show enhanced lethality compared to single Tg(Th-MYCN)41Waw expressing mice

neoplasm

increased neuroblastoma incidence ( J:294092 )

• mice develop neuroblastoma with earlier onset, higher penetrance and enhanced lethality than in single Tg(Th-MYCN)41Waw expressing mice

decreased tumor latency ( J:294092 )

• mice show earlier onset of neuroblastoma than in single Tg(Th-MYCN)41Waw expressing mice

nervous system

increased neuroblastoma incidence ( J:294092 )

• mice develop neuroblastoma with earlier onset, higher penetrance and enhanced lethality than in single Tg(Th-MYCN)41Waw expressing mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:294092

Genotype
MGI:6476983

cn3

• Allelic Composition: Alk^{tm1.1(ALK*F1174L)Heno}/Alk⁺; Tg(Mpz-cre)94Imeg/0; Tg(Th-MYCN)41Waw/0
• Genetic Background: involves: 129X1/SvJ * BALB/c * C57BL/6 * SJL

mortality/aging

decreased tumor-free survival time ( J:294092 )

• mice that develop thoracic and/or abdominal tumors die by 6 months

neoplasm

increased neuroblastoma incidence ( J:294092 )

• 17 of 18 mice develop bulky thoracic and/or abdominal tumors, with tumors showing features characteristic of neuroblastoma

• 14 of 18 mice exhibit abdominal tumors

• 4 of 18 mice exhibit thoracic tumors

• 2 of 18 mice exhibit both abdominal and thoracic tumors

nervous system

increased neuroblastoma incidence ( J:294092 )

• 17 of 18 mice develop bulky thoracic and/or abdominal tumors, with tumors showing features characteristic of neuroblastoma

• 14 of 18 mice exhibit abdominal tumors

• 4 of 18 mice exhibit thoracic tumors

• 2 of 18 mice exhibit both abdominal and thoracic tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:294092

Genotype
MGI:6196323

cx4

• Allelic Composition: Ret^tm2.1Cos/?; Tg(Th-MYCN)41Waw/0
• Genetic Background: involves: 129S1/Sv * BALB/c * C57BL/6J

mortality/aging

premature death ( J:261033 )

• mice begin to die around 100 days of age, with 50% survival at 250 days of age

neoplasm

increased neuroblastoma incidence ( J:261033 )

• mice develop stroma-poor neuroblastoma, with the majority of tumors showing signs of differentiation

nervous system

increased neuroblastoma incidence ( J:261033 )

• mice develop stroma-poor neuroblastoma, with the majority of tumors showing signs of differentiation

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:261033

Genotype
MGI:5789376

cx5

• Allelic Composition: Alk^tm2.1Ics/?; Tg(Th-MYCN)41Waw/0
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ * BALB/c * C57BL/6 * C57BL/6J

neoplasm

increased neuroblastoma incidence ( J:228124 , J:261033 )

• tumors are classified as neuroblastoma, stroma-poor, poorly differentiated or differentiating (J:228124)

• tumor onset occurs earlier than in mice carrying the Alk^tm1.1Ics allele (J:228124)

• abdominal tumors are median, perivascular and locally invasive without evidence of macroscopic tumor spread to other organs (J:228124)

• tumors at 2 or 3 locations (abdominal/thoracic/cervical) are seen in 100% of mice (J:228124)

• mice treated with vandetanib, a kinase inhibitor, show a reduction in abdominal tumor weight (J:228124)

mortality/aging

premature death ( J:261033 )

• mice begin to die after 50 days of age, with 10% survival after 150 days of age

nervous system

increased neuroblastoma incidence ( J:228124 , J:261033 )

• tumors are classified as neuroblastoma, stroma-poor, poorly differentiated or differentiating (J:228124)

• tumor onset occurs earlier than in mice carrying the Alk^tm1.1Ics allele (J:228124)

• abdominal tumors are median, perivascular and locally invasive without evidence of macroscopic tumor spread to other organs (J:228124)

• tumors at 2 or 3 locations (abdominal/thoracic/cervical) are seen in 100% of mice (J:228124)

• mice treated with vandetanib, a kinase inhibitor, show a reduction in abdominal tumor weight (J:228124)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:261033 , J:228124

Genotype
MGI:5789375

cx6

• Allelic Composition: Alk^tm1.1Ics/?; Tg(Th-MYCN)41Waw/0
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ * BALB/c * C57BL/6 * C57BL/6J

neoplasm

increased neuroblastoma incidence ( J:228124 , J:261033 )

• tumors are classified as neuroblastoma, stroma-poor, poorly differentiated or differentiating (J:228124)

• tumor onset occurs later than in mice carrying the Alk^tm2.1Ics allele (J:228124)

• abdominal tumors are median, perivascular and locally invasive without evidence of macroscopic tumor spread to other organs (J:228124)

• tumors at 2 or 3 locations (abdominal/thoracic/cervical) are seen in 70% of mice (J:228124)

• mice treated with vandetanib, a kinase inhibitor, or crizotinib, show a reduction in abdominal tumor weight (J:228124)

mortality/aging

premature death ( J:261033 )

• mice begin to die around 100 days of age, with 70% survival at 200-300 days of age

nervous system

increased neuroblastoma incidence ( J:228124 , J:261033 )

• tumors are classified as neuroblastoma, stroma-poor, poorly differentiated or differentiating (J:228124)

• tumor onset occurs later than in mice carrying the Alk^tm2.1Ics allele (J:228124)

• abdominal tumors are median, perivascular and locally invasive without evidence of macroscopic tumor spread to other organs (J:228124)

• tumors at 2 or 3 locations (abdominal/thoracic/cervical) are seen in 70% of mice (J:228124)

• mice treated with vandetanib, a kinase inhibitor, or crizotinib, show a reduction in abdominal tumor weight (J:228124)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:228124 , J:261033

Genotype
MGI:5009552

cx7

• Allelic Composition: Nf1^tm1Tyj/Nf1⁺; Tg(Th-MYCN)41Waw/0
• Genetic Background: involves: 129S2/SvPas * BALB/c * C57BL/6J

neoplasm

increased neuroblastoma incidence ( J:41126 )

• mutants exhibit a decreased latency and an increased incidence of tumors compared to single hemizygous Tg(Th-MYCN)41Waw mice, such that about 75% of mutants develop neuroblastomas by 10 months of age compared to 40% of single hemizygous Tg(Th-MYCN)41Waw mice

nervous system

increased neuroblastoma incidence ( J:41126 )

• mutants exhibit a decreased latency and an increased incidence of tumors compared to single hemizygous Tg(Th-MYCN)41Waw mice, such that about 75% of mutants develop neuroblastomas by 10 months of age compared to 40% of single hemizygous Tg(Th-MYCN)41Waw mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:41126

Genotype
MGI:5009553

cx8

• Allelic Composition: Rb1^tm1Tyj/Rb1⁺; Tg(Th-MYCN)41Waw/0
• Genetic Background: involves: 129S2/SvPas * BALB/c * C57BL/6J

neoplasm

increased neuroblastoma incidence ( J:41126 )

• mutants exhibit a decreased latency and an increased incidence of tumors compared to single hemizygous Tg(Th-MYCN)41Waw mice, such that about 75% of mutants develop neuroblastomas by 10 months of age compared to 40% of single hemizygous Tg(Th-MYCN)41Waw mice

nervous system

increased neuroblastoma incidence ( J:41126 )

• mutants exhibit a decreased latency and an increased incidence of tumors compared to single hemizygous Tg(Th-MYCN)41Waw mice, such that about 75% of mutants develop neuroblastomas by 10 months of age compared to 40% of single hemizygous Tg(Th-MYCN)41Waw mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:41106

Genotype
MGI:5009554

cx9

• Allelic Composition: Tg(Th-MYCN)41Waw/0; Trp53^tm1Brd/Trp53⁺
• Genetic Background: involves: 129S7/SvEvBrd * BALB/c * C57BL/6J * FVB/N

neoplasm

increased neuroblastoma incidence ( J:41126 )

• mutants exhibit a tumor incidence similar to that of single hemizygous Tg(Th-MYCN)41Waw mice

nervous system

increased neuroblastoma incidence ( J:41126 )

• mutants exhibit a tumor incidence similar to that of single hemizygous Tg(Th-MYCN)41Waw mice

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:41126

Genotype
MGI:5636486

cx10

• Allelic Composition: Tg(Th-ALK*F1174L)2Loch/0; Tg(Th-MYCN)41Waw/0
• Genetic Background: involves: 129X1/SvJ * BALB/c * C57BL/6J * CBA

neoplasm

increased neuroblastoma incidence ( J:191012 )

• mice develop large, bulky and locally invasive thoracic and abdominal masses arising in the paraspinal ganglia or adrenals indicative of neuroblastoma

• mice show complete tumor penetrance, shorter median time to tumor onset and decreased survival at 100 days of age compared to single Tg(Th-MYCN)41Waw hemizygous mice

• tumors show decreased level of apoptosis compared to tumors from single Tg(Th-MYCN)41Waw hemizygous mice

• mice are resistant to crizotinib treatment, showing no effect on tumor size, cellularity or apoptosis

• combined treatment with crizotinib and Torin2 (an ATP-competitive inhibitor of mTOR) reduces tumor size and growth and increases apoptosis

mortality/aging

premature death ( J:191012 )

• mice show decreased survival at 100 days of age

nervous system

increased neuroblastoma incidence ( J:191012 )

• mice develop large, bulky and locally invasive thoracic and abdominal masses arising in the paraspinal ganglia or adrenals indicative of neuroblastoma

• mice show complete tumor penetrance, shorter median time to tumor onset and decreased survival at 100 days of age compared to single Tg(Th-MYCN)41Waw hemizygous mice

• tumors show decreased level of apoptosis compared to tumors from single Tg(Th-MYCN)41Waw hemizygous mice

• mice are resistant to crizotinib treatment, showing no effect on tumor size, cellularity or apoptosis

• combined treatment with crizotinib and Torin2 (an ATP-competitive inhibitor of mTOR) reduces tumor size and growth and increases apoptosis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:191012

Genotype
MGI:5009550

tg11

• Allelic Composition: Tg(Th-MYCN)41Waw/Tg(Th-MYCN)41Waw
• Genetic Background: involves: BALB/c * C57BL/6J

neoplasm

increased neuroblastoma incidence ( J:41126 )

• homozygous mutants show increased incidence and decreased latency of neuroblastoma formation compared to hemizygous mice, with 100% of mice developing tumors at 4 months of age

nervous system

increased neuroblastoma incidence ( J:41126 )

• homozygous mutants show increased incidence and decreased latency of neuroblastoma formation compared to hemizygous mice, with 100% of mice developing tumors at 4 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:41126

Genotype
MGI:5009555

tg12

• Allelic Composition: Tg(Th-MYCN)41Waw/0
• Genetic Background: involves: 129X1/SvJ * BALB/c * C57BL/6J

Histology and immunohistochemistry of neuroblastoma Tg(Th-MYCN)41Waw/0 tumors

neoplasm

increased neuroblastoma incidence ( J:172448 )

• about 33% of mutants develop neuroblastoma in the paraspinal ganglia, but not in the adrenal

• tumors are first detected in the abdomen at 6 weeks of age and arise in the ganglion cells

• tumors show features of neuronal differentiation including dense core neurosecretory vesicles, synaptic junctions and areas of lipids throughout the tumors

• neuroblastomas resemble a class of aggressive human neuroblastoma tumors classified as large cell neuroblastoma and have molecular and cellular features of Stage 4 NMYC amplified human neuroblastoma

• 10% of tumors exhibit an arrest in growth between weeks 8-10 which last about 2 weeks and is followed by complete regression of tumors

nervous system

increased neuroblastoma incidence ( J:172448 )

• about 33% of mutants develop neuroblastoma in the paraspinal ganglia, but not in the adrenal

• tumors are first detected in the abdomen at 6 weeks of age and arise in the ganglion cells

• tumors show features of neuronal differentiation including dense core neurosecretory vesicles, synaptic junctions and areas of lipids throughout the tumors

• neuroblastomas resemble a class of aggressive human neuroblastoma tumors classified as large cell neuroblastoma and have molecular and cellular features of Stage 4 NMYC amplified human neuroblastoma

• 10% of tumors exhibit an arrest in growth between weeks 8-10 which last about 2 weeks and is followed by complete regression of tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:172448

Genotype
MGI:5009549

tg13

• Allelic Composition: Tg(Th-MYCN)41Waw/0
• Genetic Background: involves: BALB/c * C57BL/6J

neoplasm

increased neuroblastoma incidence ( J:41126 )

• mutants develop thoracic paraspinous masses that histology indicates as neuroblastomas

• tumors show varying degrees of neuronal differentiation

• tumors show gains and losses of chromosomal regions; most commonly gained regions are on chromosomes 11 and 17, while loss is associated most often with chromosomes 5, 9, 16 and X

• Background Sensitivity: tumor penetrance on a background involving BALB/c and C57BL/6J is greater than in mutants with a BALB/c, C57BL/6J and FVB/N background

nervous system

increased neuroblastoma incidence ( J:41126 )

• mutants develop thoracic paraspinous masses that histology indicates as neuroblastomas

• tumors show varying degrees of neuronal differentiation

• tumors show gains and losses of chromosomal regions; most commonly gained regions are on chromosomes 11 and 17, while loss is associated most often with chromosomes 5, 9, 16 and X

• Background Sensitivity: tumor penetrance on a background involving BALB/c and C57BL/6J is greater than in mutants with a BALB/c, C57BL/6J and FVB/N background

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:41126

Genotype
MGI:5009551

tg14

• Allelic Composition: Tg(Th-MYCN)41Waw/0
• Genetic Background: involves: BALB/c * C57BL/6J * FVB/N

neoplasm

increased neuroblastoma incidence ( J:41126 )

• Background Sensitivity: tumor penetrance on a BALB/c, C57BL/6J and FVB/N background is less than in mutants on a BALB/c and C57BL/6J background only

nervous system

increased neuroblastoma incidence ( J:41126 )

• Background Sensitivity: tumor penetrance on a BALB/c, C57BL/6J and FVB/N background is less than in mutants on a BALB/c and C57BL/6J background only

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neuroblastoma		DOID:769		J:141126