Analysis Tools
normal phenotype
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• these mice were fertile and exhibited normal testicular development and spermatogenesis
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Allele Symbol Allele Name Allele ID |
Tg(Dhh-cre)1Mejr transgene insertion 1, Dies Meijer MGI:4359600 |
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| Summary |
29 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• these mice were fertile and exhibited normal testicular development and spermatogenesis
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• axons of peripheral nerves are hypermyelinated at P90
• however, mice show normal numbers of Schwann cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice show myelination defects similar to single conditional Ptpn11tm1.1Wbm homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at P15, the myelin of peripheral axons is thinner but axons are hypermyelinated at P90
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• at P15 and P90, 36.7% and 17.8% of axons with diameters >1 um are nonmyelinated, respectively compared to 3.5% and 0.8% in controls
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• axons are hypermyelinated at P90
• however, mice show rescue of Schwann cell development and Schwan cells are able to myelinate
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• most mice die by 5 weeks of age
• all mice die by 7 weeks of age
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• increased in the sciatic nerve
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• increased in the sciatic nerve
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• as determined by marker expression, Schwann cells do not progress beyond the immature stage unlike wild-type cells
• between P8 and P32, the number of Schwann cells in the sciatic nerve is increased slightly compared to in wild-type mice
• Schwann cells contain high amounts of rough endoplasmic reticulum compared to in wild-type mice
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• sciatic nerves are translucent, less well defined, lacks myelination, and lacks the characteristic banded pattern compared with sciatic nerves from wild-type mice
• the number of cells in the sciatic nerve is increased compared to in wild-type mice
• between P8 and P32, the number of Schwann cells in the sciatic nerve is increased slightly compared to in wild-type mice
• from P16 to P32, sciatic nerves contain increased endothelial cells, pericytes, macrophages, T lymphocytes, perineurial cells, endoneurial fibroblast, and adipocytes compared in wild-type mice
• sciatic nerves contain a dense layer of collagen and elastic fibers unlike in wild-type mice
• at P16 and P32, Remak bundles within the sciatic nerve are absent unlike in wild-type mice
• the perineural sheath is thinner than in wild-type mice
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• in the sciatic nerve
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• sciatic nerves compound action potentials lack the fast component unlike in wild-type mice
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• in the sciatic nerve
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• mice develop a straddled position of the hindlimbs unlike wild-type mice
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• mice exhibit progressive deterioration of locomotion unlike wild-type mice
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• staggering gait
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• beginning at P8
• 52% lighter at P24
• 68% lighter at P32
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• mice fail to thrive shortly after birth
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• increased in the sciatic nerve
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• increased in the sciatic nerve
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• animals are normal and healthy; sciatic nerves of P8 mice show no obvious morphological abnormalities
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• disruption of entry into the myelination program of remaining Schwann cells
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at P56 and P120 (about 55% and 25%), respectively, of nerves are abnormal with many promyelin configurations
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• at P16 nerves contain many promyelin configurations in contrast to wild type and heterozygotes in which >90% of large-caliber axons are myelinated
• at P56 and P120, abnormal axons are thinly myelinated resembling wild-type nerves during the first postnatal week
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• testis size is slightly decreased in P14 mutants
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| N |
• spermatogenesis is normal; Sertoli cell location is normal
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• testis size is slightly decreased in P14 mutants
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice display a similar peripheral nervous system phenotype as homozygous Ptentm2.1Ppp Tg(Dhh-cre)1Mejr/0 mice, except with a latency of 415 days
• 100% exhibit enlarged branchial plexi
• 20% exhibit enlarged sacral plexi
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• enlarged peripheral nerves are graded as hyperplasia to low-grade grade peripheral nerve sheath tumors (PNSTs)
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• 100% exhibit enlarged trigeminal nerves
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• 80% exhibit enlarged sciatic nerves
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• enlarged peripheral nerves are graded as hyperplasia to low-grade grade peripheral nerve sheath tumors (PNSTs)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• rapid postnatal death, with a medial survival age of 26 days
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• 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
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• enlarged peripheral nerves are graded as high-grade grade peripheral nerve sheath tumors (PNSTs) resembling human sporatic malignant grade peripheral nerve sheath tumors
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• 92% exhibit enlarged trigeminal nerves
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• mutants exhibit multiple enlarged dorsal root ganglia
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• 50% exhibit enlarged sciatic nerves
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• enlarged peripheral nerves are graded as high-grade grade peripheral nerve sheath tumors (PNSTs) resembling human sporatic malignant grade peripheral nerve sheath tumors
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| malignant peripheral nerve sheath tumor | DOID:5940 | J:195067 | ||
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• median survival age is 247 days compared to conditional Pten heterozygotes that have a median survival age of 415 days
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• mutants exhibit a similar peripheral nervous system phenotype as triple homozygous Ptentm2.1Ppp Tg(Dhh-cre)1Mejr/0 Tg(Cnp-EGFR)10Nrat/0 mutants but with delayed latency and reduced tumor multiplicity
• 100% exhibit enlarged branchial plexi
• 10% exhibit enlarged sacral plexi
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• enlarged peripheral nerves are low-grade peripheral nerve sheath tumors (PNSTs)
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• 90% exhibit enlarged trigeminal nerves
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• 80% exhibit enlarged sciatic nerves
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• enlarged peripheral nerves are low-grade peripheral nerve sheath tumors (PNSTs)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• although the abundance of SEPTIN9 is markedly reduced in sciatic nerve lysates as expected, the abundance and localization of other septin subunits expressed in PNS myelin (SEPTIN2, SEPTIN7, SEPTIN8 and SEPTIN11) are similar to those in sciatic nerve lysates of control mice
• P14 sciatic nerves show no significant change in the number of normal-appearing myelinated axons; no axonal degeneration is noted and the number of myelin outfoldings is similar to that in control mice, indicating normal biogenesis of PNS myelin
• P75 sciatic nerves show similar abundance of myelin proteins (MAG, CNP, P0/MPZ, PMP22) relative to control mice
• mice exhibit normal motor nerve conduction velocity (mNCV) in sciatic nerves and normal sensory nerve conduction velocity (sNCV) in the tail nerve at 6 months of age
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| N |
• mice show no alterations in the latency of retracting a hindpaw upon a mechanical stimulus (plantar test) at P45 or in the latency of falling from an accelerating rotating rod at 2.5 months of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• paralysis in one or both hind limbs begins at approximately 4 months of age, with 55.6% of mice showing paralysis by 5 months of age
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• 81.5% of mice exhibit neurofibroma tumors; tumors arise at the dorsal root ganglia, with invasion of the neural foramen and lead to compression of the spinal cord
• most tumors are detected in cervical and thoracic spine, with a lower percentage in the lumbar spine
• neurofibromas are characterized by disorganized Remak bundles and enriched deposition of collagen
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• 81.5% of mice exhibit neurofibroma tumors; tumors arise at the dorsal root ganglia, with invasion of the neural foramen and lead to compression of the spinal cord
• most tumors are detected in cervical and thoracic spine, with a lower percentage in the lumbar spine
• neurofibromas are characterized by disorganized Remak bundles and enriched deposition of collagen
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• enlarged peripheral nerves
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• enlarged spinal nerve roots
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| neurofibromatosis 1 | DOID:0111253 |
OMIM:162200 |
J:234172 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• paralysis in one or both hind limbs begins at approximately 4 months of age, with 54.1% of mice showing paralysis by 5 months of age
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• 79.2% of mice exhibit neurofibroma tumors; tumors arise at the dorsal root ganglia, with invasion of the neural foramen and lead to compression of the spinal cord
• most tumors are detected in cervical and thoracic spine, with a lower percentage in the lumbar spine
• neurofibromas are characterized by disorganized Remak bundles and enriched deposition of collagen
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• 79.2% of mice exhibit neurofibroma tumors; tumors arise at the dorsal root ganglia, with invasion of the neural foramen and lead to compression of the spinal cord
• most tumors are detected in cervical and thoracic spine, with a lower percentage in the lumbar spine
• neurofibromas are characterized by disorganized Remak bundles and enriched deposition of collagen
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• enlarged peripheral nerves
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• enlarged spinal nerve roots and lesions in sciatic nerves showing abnormal nonmyelinating axons
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| neurofibromatosis 1 | DOID:0111253 |
OMIM:162200 |
J:234172 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• P14 sciatic nerves show no significant change in the number of normal-appearing myelinated axons; no axonal degeneration is noted and the number of myelin outfoldings is similar to that in control mice, indicating normal biogenesis of PNS myelin
• P75 sciatic nerves show similar abundance of myelin proteins (MAG, CNP, P0/MPZ, PMP22) relative to control mice
• motor nerve conduction velocity (mNCV) in sciatic nerves and sensory nerve conduction velocity (sNCV) in the tail nerve are slightly but not significantly decreased at 1 year of age
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• while the abundance of SEPTIN2 is markedly reduced in sciatic nerve lysates as expected, the abundance of other septin subunits expressed in PNS myelin (SEPTIN7, SEPTIN8, SEPTIN9, and SEPTIN11) is also substantially lower than that in the sciatic nerve lysates of control mice
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• mice show no alterations in the latency of retracting a hindpaw upon a mechanical stimulus (plantar test) at 32 weeks of age or in the latency of falling from an accelerating rotating rod at 6 months of age
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal internode length and nodal and paranodal dimensions
• normal neurofilament density and phosphorylation
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• increased diameter of phrenic and ventral tail nerve axons
• increased diameter of non-myelinated sciatic nerve axons in Remak bundles at ages P9 and 2 months
• normal myelin sheath thickness to axon diameter ratio for phrenic and ventral tail nerve axons
• normal number of axons per Remak bundle, with no axon diameters larger than 1 micrometer
• normal frequency of developmentally sorted promyelinated axons
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• increased sensory nerve action potential (SNAP)
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• increased sensory nerve conduction velocity (SNCV)
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• increased slipping when walking over a regular grid
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• accelerated reaction in hot plate test
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• absence of spontaneous apnea
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• in the sciatic nerve at P12 similar to Lgi4clp homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice display no locomotor deficit in the accelerated rotarod and open field tests relative to control mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• myelin abnormalities including tomacula, redundant myelin, and outfolds
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• at P9 Sertoli cells are randomly distributed unlike in controls
• at P14 tubules lack luminal space and are instead filled with a poorly organized mix of Sertoli cells and differentiating germ cells
• at P28 tubules contain no apparent germ cells and are filled with randomized, unpolarized Sertoli cells with immature morphology
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• Sertoli cells fail to migrate properly and retain an immature morphology at P28
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• by P9 the distribution of germs cells is highly abnormal with more cells in the center and fewer cells at the periphery of the tubules
• meiosis initiates but germ cells are absent by P28
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• at P9 Sertoli cells are randomly distributed unlike in controls
• at P14 tubules lack luminal space and are instead filled with a poorly organized mix of Sertoli cells and differentiating germ cells
• at P28 tubules contain no apparent germ cells and are filled with randomized, unpolarized Sertoli cells with immature morphology
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• Sertoli cells fail to migrate properly and retain an immature morphology at P28
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• by P9 the distribution of germs cells is highly abnormal with more cells in the center and fewer cells at the periphery of the tubules
• meiosis initiates but germ cells are absent by P28
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• rarely observe aberrantly myelinated small axons in mutants and the ratio of nonmyelinated to myelinated axons is unchanged
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• transient acceleration of postnatal myelination
• however, adult myelination is normal
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• following nerve axotomy or sciatic nerve crush, mice exhibit reduced myelin degradation and increases remyelination compared with wild-type mice
• however, sciatic function index and Von Frey threshold are normal after nerve crush
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal Kv1 channel complex protein at the juxtaparanodal membrane in sciatic nerves
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• aberrant myelin formation and myelin in peripheral nerves
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 04/23/2024 MGI 6.23 |
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