Phenotypes associated with this allele
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(CAG-Alk*F1174L,-luc)60Jhsc mutation
(0 available)
Tg(Dbh-icre)1Gsc mutation
(0 available)
Tg(Th-MYCN)41Waw mutation
(2 available)
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neoplasm
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• 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
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nervous system
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• 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
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Alktm1.1(ALK*F1174L)Heno mutation
(0 available);
any
Alk mutation
(62 available)
Tg(Mpz-cre)94Imeg mutation
(0 available)
Tg(Th-MYCN)41Waw mutation
(2 available)
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mortality/aging
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• mice show enhanced lethality compared to single Tg(Th-MYCN)41Waw expressing mice
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neoplasm
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• mice develop neuroblastoma with earlier onset, higher penetrance and enhanced lethality than in single Tg(Th-MYCN)41Waw expressing mice
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• mice show earlier onset of neuroblastoma than in single Tg(Th-MYCN)41Waw expressing mice
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nervous system
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• mice develop neuroblastoma with earlier onset, higher penetrance and enhanced lethality than in single Tg(Th-MYCN)41Waw expressing mice
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Alktm1.1(ALK*F1174L)Heno mutation
(0 available);
any
Alk mutation
(62 available)
Tg(Mpz-cre)94Imeg mutation
(0 available)
Tg(Th-MYCN)41Waw mutation
(2 available)
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mortality/aging
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• mice that develop thoracic and/or abdominal tumors die by 6 months
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neoplasm
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• 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
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nervous system
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• 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
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rettm2.1Cos mutation
(1 available);
any
Ret mutation
(53 available)
Tg(Th-MYCN)41Waw mutation
(2 available)
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mortality/aging
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• mice begin to die around 100 days of age, with 50% survival at 250 days of age
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neoplasm
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• mice develop stroma-poor neuroblastoma, with the majority of tumors showing signs of differentiation
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nervous system
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• mice develop stroma-poor neuroblastoma, with the majority of tumors showing signs of differentiation
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Alktm2.1Ics mutation
(0 available);
any
Alk mutation
(62 available)
Tg(Th-MYCN)41Waw mutation
(2 available)
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neoplasm
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• tumors are classified as neuroblastoma, stroma-poor, poorly differentiated or differentiating
(J:228124)
• tumor onset occurs earlier than in mice carrying the Alktm1.1Ics 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)
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mortality/aging
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• mice begin to die after 50 days of age, with 10% survival after 150 days of age
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nervous system
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• tumors are classified as neuroblastoma, stroma-poor, poorly differentiated or differentiating
(J:228124)
• tumor onset occurs earlier than in mice carrying the Alktm1.1Ics 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)
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Alktm1.1Ics mutation
(0 available);
any
Alk mutation
(62 available)
Tg(Th-MYCN)41Waw mutation
(2 available)
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neoplasm
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• tumors are classified as neuroblastoma, stroma-poor, poorly differentiated or differentiating
(J:228124)
• tumor onset occurs later than in mice carrying the Alktm2.1Ics 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)
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mortality/aging
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• mice begin to die around 100 days of age, with 70% survival at 200-300 days of age
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nervous system
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• tumors are classified as neuroblastoma, stroma-poor, poorly differentiated or differentiating
(J:228124)
• tumor onset occurs later than in mice carrying the Alktm2.1Ics 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)
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neoplasm
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• 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
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nervous system
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• 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
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neoplasm
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• 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
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nervous system
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• 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
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Th-MYCN)41Waw mutation
(2 available)
Trp53tm1Brd mutation
(5 available);
any
Trp53 mutation
(232 available)
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neoplasm
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• mutants exhibit a tumor incidence similar to that of single hemizygous Tg(Th-MYCN)41Waw mice
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nervous system
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• mutants exhibit a tumor incidence similar to that of single hemizygous Tg(Th-MYCN)41Waw mice
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Th-ALK*F1174L)2Loch mutation
(0 available)
Tg(Th-MYCN)41Waw mutation
(2 available)
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neoplasm
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• 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
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mortality/aging
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• mice show decreased survival at 100 days of age
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nervous system
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• 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
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Th-MYCN)41Waw mutation
(2 available)
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neoplasm
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• 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
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nervous system
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• 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
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Allelic
Composition |
Tg(Th-MYCN)41Waw/0
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Genetic
Background |
involves: 129X1/SvJ * BALB/c * C57BL/6J |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Th-MYCN)41Waw mutation
(2 available)
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Histology and immunohistochemistry of neuroblastoma Tg(Th-MYCN)41Waw/0 tumors
neoplasm
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• 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
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nervous system
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• 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
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Allelic
Composition |
Tg(Th-MYCN)41Waw/0
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Genetic
Background |
involves: BALB/c * C57BL/6J |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Th-MYCN)41Waw mutation
(2 available)
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neoplasm
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• 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
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nervous system
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• 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
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Allelic
Composition |
Tg(Th-MYCN)41Waw/0
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Genetic
Background |
involves: BALB/c * C57BL/6J * FVB/N |
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| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Th-MYCN)41Waw mutation
(2 available)
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neoplasm
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• 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
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nervous system
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• 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
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Analysis Tools