Phenotypes associated with this allele

• Allele Symbol: Tg(Cnp-EGFR)10Nrat
• Allele Name: transgene insertion 10, Nancy Ratner
• Allele ID: MGI:5485351
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Pten^tm2.1Ppp/Pten^tm2.1Ppp Tg(Cnp-EGFR)10Nrat/0 Tg(Dhh-cre)1Mejr/0	involves: 129S1/Sv * C57BL/6 * FVB/N * SJL	MGI:5485414
cn2	Pten^tm2.1Ppp/Pten^+ Tg(Cnp-EGFR)10Nrat/0 Tg(Dhh-cre)1Mejr/0	involves: 129S1/Sv * C57BL/6 * FVB/N * SJL	MGI:5485415
cx3	Nf1^tm1Fcr/Nf1^+ Tg(Cnp-EGFR)10Nrat/0	involves: 129S/SvEv * C57BL/6 * SJL	MGI:5485353
tg4	Tg(Cnp-EGFR)10Nrat/0	involves: C57BL/6 * SJL	MGI:5485352

Genotype
MGI:5485414

cn1

• Allelic Composition: Pten^tm2.1Ppp/Pten^tm2.1Ppp; Tg(Cnp-EGFR)10Nrat/0; Tg(Dhh-cre)1Mejr/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * FVB/N * SJL

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

mortality/aging

premature death ( J:195067 )

• rapid postnatal death, with a medial survival age of 26 days

nervous system

abnormal nervous system morphology ( J:195067 )

• mutants exhibit enlarged peripheral nerves: brachial plexi, sacral plexi, trigeminal and sciatic nerves

• 100% exhibit enlarged branchial plexi

• 50% exhibit enlarged lumbar sacral plexi

• mast cells are seen in enlarged peripheral nerves

increased neurofibrosarcoma incidence ( J:195067 )

• enlarged peripheral nerves are graded as high-grade grade peripheral nerve sheath tumors (PNSTs) resembling human sporatic malignant grade peripheral nerve sheath tumors

abnormal trigeminal nerve morphology ( J:195067 )

• 92% exhibit enlarged trigeminal nerves

enlarged dorsal root ganglion ( J:195067 )

• mutants exhibit multiple enlarged dorsal root ganglia

abnormal sciatic nerve morphology ( J:195067 )

• 50% exhibit enlarged sciatic nerves

neoplasm

increased neurofibrosarcoma incidence ( J:195067 )

• enlarged peripheral nerves are graded as high-grade grade peripheral nerve sheath tumors (PNSTs) resembling human sporatic malignant grade peripheral nerve sheath tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
malignant peripheral nerve sheath tumor		DOID:5940		J:195067

Genotype
MGI:5485415

cn2

• Allelic Composition: Pten^tm2.1Ppp/Pten⁺; Tg(Cnp-EGFR)10Nrat/0; Tg(Dhh-cre)1Mejr/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * FVB/N * SJL

nervous system

abnormal nervous system morphology ( J:195067 )

• mice display a similar peripheral nervous system phenotype as homozygous Pten^tm2.1Ppp Tg(Dhh-cre)1Mejr/0 mice, except with a latency of 415 days

• 100% exhibit enlarged branchial plexi

• 20% exhibit enlarged sacral plexi

increased neurofibrosarcoma incidence ( J:195067 )

• enlarged peripheral nerves are graded as hyperplasia to low-grade grade peripheral nerve sheath tumors (PNSTs)

abnormal trigeminal nerve morphology ( J:195067 )

• 100% exhibit enlarged trigeminal nerves

abnormal sciatic nerve morphology ( J:195067 )

• 80% exhibit enlarged sciatic nerves

neoplasm

increased neurofibrosarcoma incidence ( J:195067 )

• enlarged peripheral nerves are graded as hyperplasia to low-grade grade peripheral nerve sheath tumors (PNSTs)

Genotype
MGI:5485353

cx3

• Allelic Composition: Nf1^tm1Fcr/Nf1⁺; Tg(Cnp-EGFR)10Nrat/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * SJL

nervous system

abnormal nervous system morphology ( J:95933 )

• mutants exhibit similar diffuse nerve enlargement as in single Tg(Cnp-EGFR)10Nrat mice

abnormal somatic nervous system morphology ( J:95933 )

• saphenous nerves are larger at 4 months of age compared to wild-type mice but similar in size to those in single Tg(Cnp-EGFR)10Nrat mice

neoplasm

decreased tumor incidence ( J:95933 )

• no tumors are detected compared to single Tg(Cnp-EGFR)10Nrat mice

Genotype
MGI:5485352

tg4

• Allelic Composition: Tg(Cnp-EGFR)10Nrat/0
• Genetic Background: involves: C57BL/6 * SJL

nervous system

abnormal nervous system morphology ( J:95933 )

• increase in size of peripheral nerves results from an increase in the number nerve Schwann cells, increased collagen and increased myelin thickness

• collagen fibers fill the nerve matrix between large myelinated axons and are frequently errantly wrapped by Schwann cell processes

increased neurofibroma incidence ( J:95933 )

• mutants develop rare nerve tumors, with one mouse showing a grossly enlarged spinal nerve root diagnosed as a neurofibroma

abnormal Schwann cell morphology ( J:95933 )

• saphenous nerves are abnormal in 4 month old mutants, with non-myelin-forming Schwann cells showing long aberrant processes that wrap one or two, or no, small axons, indicating that Schwann cells wrap progressively fewer axons and show progressive dissociation of non-myelin-forming Schwann cells from axons

• Schwann cells erroneously wrap collagen fibers in the nerve matrix

increased Schwann cell number ( J:95933 )

• Schwann cell hyperplasia as indicated by an increase in numbers of endoneurial cells in nerves

• Schwann cell hyperplasia precedes mast cell accumulation

abnormal neurite morphology ( J:95933 )

• nerves exhibit increased fibrosis

abnormal myelin sheath morphology ( J:95933 )

• the distance between myelin sheaths in saphenous nerves is increased

increased myelin sheath thickness ( J:95933 )

• myelin sheath thickness of saphenous nerves is increased

abnormal somatic nervous system morphology ( J:95933 )

• intercostal nerves, sciatic nerves, cauda equina, cranial nerves, and cutaneous nerves exhibit diffuse hypertrophy

• 2- to 8-fold increase in the number of nuclei in nerve cross sections, indicating increased hypercellularity in nerves

• saphenous nerves show up to an 8-fold increase in nerve cross-sectional area and harbor on average 499 large axons compared to 465 in controls

abnormal cranial nerve morphology ( J:95933 )

• diffuse hypertrophy

abnormal sciatic nerve morphology ( J:95933 )

• diffuse hypertrophy

peripheral nervous system degeneration ( J:95933 )

• the nerve pathology worsens with time; nerves progressively accumulate collagen and dysfunctional Schwann cells and have increasing numbers of disrupted small axonal fiber bundles, suggesting degenerative neuropathy of small caliber axons

neoplasm

increased rhabdomyosarcoma incidence ( J:95933 )

• mutants develop rare nerve tumors, with one mouse showing a nerve-associated spindle cell tumor identified as a triton rhabdomyosarcoma

increased neurofibroma incidence ( J:95933 )

• mutants develop rare nerve tumors, with one mouse showing a grossly enlarged spinal nerve root diagnosed as a neurofibroma

increased malignant triton tumor incidence ( J:95933 )

• mutants develop rare nerve tumors, with one mouse showing a nerve-associated spindle cell tumor with muscle differentiation and identified as a triton rhabdomyosarcoma tumor

hematopoietic system

increased mast cell number ( J:95933 )

• nerves exhibit increased mast cell infiltration; mast cells are degranulating

immune system

increased mast cell number ( J:95933 )

• nerves exhibit increased mast cell infiltration; mast cells are degranulating

muscle

increased rhabdomyosarcoma incidence ( J:95933 )

• mutants develop rare nerve tumors, with one mouse showing a nerve-associated spindle cell tumor identified as a triton rhabdomyosarcoma