Phenotypes associated with this allele

• Allele Symbol: Cnp^tm1(cre)Kan
• Allele Name: targeted mutation 1, Klaus-Armin Nave
• Allele ID: MGI:3051635
• Summary: 26 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cnp^tm1(cre)Kan/Cnp^tm1(cre)Kan	B6N.129-Cnp^tm1(cre)Kan	MGI:5902385
hm2	Cnp^tm1(cre)Kan/Cnp^tm1(cre)Kan	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3051754
cn3	Cmtm5^tm1c(KOMP)Wtsi/Cmtm5^tm1c(KOMP)Wtsi Cnp^tm1(cre)Kan/Cnp^+	B6.Cg-Cnp^tm1(cre)Kan Cmtm5^tm1c(KOMP)Wtsi	MGI:7331498
cn4	Cnp^tm1(cre)Kan/Cnp^+ Pten^tm1Hwu/Pten^tm1Hwu	B6N.129-Cnp^tm1(cre)Kan Pten^tm1Hwu	MGI:5902387
cn5	Cnp^tm1(cre)Kan/Cnp^+ Septin8^tm1c(EUCOMM)Wtsi/Septin8^tm1c(EUCOMM)Wtsi	B6N.Cg-Septin8^tm1c(EUCOMM)Wtsi Cnp^tm1(cre)Kan	MGI:5902374
cn6	Abcd1^tm1Kan/Y Gt(ROSA)26Sor^tm2.1(CAG-ELOVL1)Geno/Gt(ROSA)26Sor^+ Cnp^tm1(cre)Kan/Cnp^+	involves: 129 * 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:6194786
cn7	Fa2h^tm1Hama/Fa2h^tm1Hama Cnp^tm1(cre)Kan/Cnp^+	involves: 129 * C57BL/6	MGI:4999602
cn8	Gt(ROSA)26Sor^tm1(DTA)Riet/Gt(ROSA)26Sor^+ Cnp^tm1(cre)Kan/Cnp^+	involves: 129P2/OlaHsd	MGI:3055718
cn9	Myrf^tm1Barr/Myrf^tm1Barr Cnp^tm1(cre)Kan/Cnp^+	involves: 129P2/OlaHsd * 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6	MGI:3852096
cn10	Gt(ROSA)26Sor^tm2(DTA)Riet/Gt(ROSA)26Sor^+ Cnp^tm1(cre)Kan/Cnp^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:3653839
cn11	Erbb3^tm2Cbm/Erbb3^tm3Cbm Erbb4^tm1Fej/Erbb4^tm1Fej Cnp^tm1(cre)Kan/?	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:3835562
cn12	Fdft1^tm1Kan/Fdft1^tm1Kan Cnp^tm1(cre)Kan/Cnp^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ	MGI:3580007
cn13	Drp2^tm1.1Brp/Y Cnp^tm1(cre)Kan/Cnp^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5431958
cn14	Pten^tm1Hwu/Pten^tm1Hwu Cnp^tm1(cre)Kan/Cnp^+	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ	MGI:4836647
cn15	Anln^tm1c(EUCOMM)Wtsi/Anln^tm1c(EUCOMM)Wtsi Cnp^tm1(cre)Kan/Cnp^+	involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6N	MGI:6360217
cn16	Septin2^tm1c(EUCOMM)Wtsi/Septin2^tm1c(EUCOMM)Wtsi Cnp^tm1(cre)Kan/Cnp^+	involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6N	MGI:7523331
cn17	Cnp^tm1(cre)Kan/Cnp^+ Tfam^tm1Lrsn/Tfam^tm1Lrsn	involves: 129S1/Sv * 129X1/SvJ	MGI:5749838
cn18	Pex5^tm1Pec/Pex5^tm1Pec Cnp^tm1(cre)Kan/Cnp^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3851811
cn19	Nfasc^tm1Bhat/Nfasc^tm1Bhat Cnp^tm1(cre)Kan/?	involves: 129S1/Sv * 129X1/SvJ	MGI:3836428
cn20	Nfasc^tm2Bhat/Nfasc^tm2Bhat Cnp^tm1(cre)Kan/Cnp^+	involves: 129S1/Sv * 129X1/SvJ	MGI:4838222
cn21	Septin9^tm2.1Emfu/Septin9^tm2.1Emfu Cnp^tm1(cre)Kan/Cnp^+	involves: 129S1/Sv * 129X1/SvJ	MGI:7523327
cn22	Zfp24^tm1.1Pop/Zfp24^tm1.1Pop Cnp^tm1(cre)Kan/Cnp^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:4429677
cn23	Hsd17b4^tm2Baes/Hsd17b4^tm2Baes Cnp^tm1(cre)Kan/Cnp^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:5523949
cn24	Plp1^tm1c(EUCOMM)Wtsi/Y Cnp^tm1(cre)Kan/Cnp^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6N	MGI:6160757
cn25	Mtor^tm1Koz/Mtor^tm1Koz Cnp^tm1(cre)Kan/Cnp^+	involves: 129S4/SvJae * C57BL/6	MGI:4820603
cx26	Plp1^tm1Kan/Y Cnp^tm1(cre)Kan/Cnp^+	involves: 129S1/Sv * 129X1/SvJ	MGI:6160760

Genotype
MGI:5902385

hm1

• Allelic Composition: Cnp^tm1(cre)Kan/Cnp^tm1(cre)Kan
• Genetic Background: B6N.129-Cnp^tm1(cre)Kan

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

nervous system

tomacula ( J:236408 )

♂

axon degeneration ( J:236408 )

♂

dysmyelination ( J:236408 )

♂ • swellings of the inner tongue of myelin

Genotype
MGI:3051754

hm2

• Allelic Composition: Cnp^tm1(cre)Kan/Cnp^tm1(cre)Kan
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

mortality/aging

premature death ( J:91814 )

• most mutants die between 7 and 11 months

behavior/neurological

ataxia ( J:91814 )

• around 4 months of age mutants develop ataxia

abnormal gait ( J:91814 )

• obvious gait abnormalities are seen

hindlimb paralysis ( J:91814 )

• round 4 months impaired hindlimb movement that develops into hindlimb paralysis by about 6 months of age is seen

• mutants between 9 and 15 months of age are unable to balance on a round bar for more than a few seconds

convulsive seizures ( J:91814 )

• around 4 months of age mutants develop convulsions when lifted by the tail

growth/size/body

weight loss ( J:91814 )

• weight loss is seen in older mutants

muscle

muscle weakness ( J:91814 )

• mutants between 9 and 15 months of age display muscle weakness

skeleton

kyphosis ( J:91814 )

• kyphosis is seen in older mutants

nervous system

convulsive seizures ( J:91814 )

• around 4 months of age mutants develop convulsions when lifted by the tail

gliosis ( J:91814 )

• reactive astrogliosis is seen in the corpus callosum and to a lesser extent in the spinal cord

• reactive microglia are seen in the corpus callosum and the white matter of the cerebellum and to a lesser extent in the spinal cord

• microglial activation can be seen by 3.5 months of age

axon degeneration ( J:91814 )

• axonal swellings with attenuated myelin sheaths and axon loss are seen in 7 month old mutants

• white matter tracts and overall brain size are reduced in 7 month old mutants

Genotype
MGI:7331498

cn3

• Allelic Composition: Cmtm5^{tm1c(KOMP)Wtsi}/Cmtm5^{tm1c(KOMP)Wtsi}; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: B6.Cg-Cnp^tm1(cre)Kan Cmtm5^{tm1c(KOMP)Wtsi}

nervous system

microgliosis ( J:327261 )

• concentration of myo-inositol is increased in the corpus callosi at 8 months of age, indicating gliosis

astrocytosis ( J:327261 )

• late-onset astrogliosis

abnormal axon morphology ( J:327261 )

• mice show early-onset progressive axonopathy, with optic nerves showing pathological axonal profiles already at P30 and their number progressively increasing

• mice show a trend toward reduced axon density is seen at P30 and P75 which reaches significance at 12 months of age and leads to axonal loss

• dorsal white matter in spinal cords shows axonopathy in 12-month-old mice

• however, mice show normal axonal diameters in the optic nerves

axon degeneration ( J:327261 )

• number of myelin whorls (multilamellar structures that display the periodicity of CNS myelin devoid of a discernible axon; i.e. remnants of degenerating myelinated fibers with relative sparing of myelin membranes) is increased in optic nerves of 12-month-old mice, indicating axonal degeneration but not myelin pathology

• however, mice show normal myelin biogenesis and composition and numbers of myelin outfoldings, normal myelin sheath thickness, unchanged inner-tongue inclusions and axoplasmic inclusions, and normal mature oligodendrocytes

vision/eye

abnormal visual evoked potential ( J:327261 )

• visually evoked potential amplitudes are reduced indicating that transmission of signals via the optic nerves to the visual cortex is impaired

• however, mice show sizeable visually evoked potentials with normal thresholds and latency, indicating normal speed of action potential propagation

• electroretinography shows normal ERG waveforms, thresholds, and amplitudes of a- and b-waves at 8.5 months of age indicating normal retinal function

hematopoietic system

microgliosis ( J:327261 )

• concentration of myo-inositol is increased in the corpus callosi at 8 months of age, indicating gliosis

immune system

microgliosis ( J:327261 )

• concentration of myo-inositol is increased in the corpus callosi at 8 months of age, indicating gliosis

behavior/neurological

behavior/neurological phenotype ( J:327261 )

N • mice show no obvious behavioral phenotype

Genotype
MGI:5902387

cn4

• Allelic Composition: Cnp^tm1(cre)Kan/Cnp⁺; Pten^tm1Hwu/Pten^tm1Hwu
• Genetic Background: B6N.129-Cnp^tm1(cre)Kan Pten^tm1Hwu

nervous system

tomacula ( J:236408 )

♂

Genotype
MGI:5902374

cn5

• Allelic Composition: Cnp^tm1(cre)Kan/Cnp⁺; Septin8^{tm1c(EUCOMM)Wtsi}/Septin8^{tm1c(EUCOMM)Wtsi}
• Genetic Background: B6N.Cg-Septin8^{tm1c(EUCOMM)Wtsi} Cnp^tm1(cre)Kan
• Cell Lines: EPD0060_3_G04

nervous system

nervous system phenotype ( J:236408 )

♂N • mice exhibit normal developmental myelination

tomacula ( J:236408 )

♂ • in adult mice but not at P15

decreased nerve conduction velocity ( J:236408 )

♂

Genotype
MGI:6194786

cn6

• Allelic Composition: Abcd1^tm1Kan/Y; Gt(ROSA)26Sor^{tm2.1(CAG-ELOVL1)Geno}/Gt(ROSA)26Sor⁺; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129 * 129S1/Sv * 129X1/SvJ * C57BL/6J

homeostasis/metabolism

increased fatty acids level ( J:257393 )

♂ • mice exhibit very-long-chain fatty acid accumulation in different lipid classes and acylcarnitines

♂ • C26:0 levels are increased 15-fold in brain and 12-fold in spinal cord

♂ • 1-hexacosanoyl-sn-glycero-3-phosophocholine (C26:0-lysoPC) levels are increased 13-fold in the brain, 24-fold in the spinal cord, and 17-fold in the blood

♂ • C26:0-carnitine levels are increased 40-fold in brain, 33-fold in spinal cord, and 16-fold in the blood

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
adrenoleukodystrophy		DOID:10588	OMIM:300100	J:257393

Genotype
MGI:4999602

cn7

• Allelic Composition: Fa2h^tm1Hama/Fa2h^tm1Hama; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129 * C57BL/6

nervous system

abnormal cerebellum morphology ( J:171655 )

• histological abnormalities are similar to those in germline null mice

• decrease in myelin lipid levels in the cerebellum compared to controls at 12 months of age but not at 6 months of age

abnormal Purkinje cell morphology ( J:171655 )

• while the overall number of Purkinje cells is similar to controls, regions with smaller sized or absent Purkinje neurons relative to controls are seen

decreased Purkinje cell size ( J:171655 )

homeostasis/metabolism

abnormal lipid level ( J:171655 )

• decrease in myelin lipid levels in the cerebellum compared to controls at 12 months of age but not at 6 months of age

abnormal galactolipid level ( J:171655 )

• hFA-GalCer galactolipids are absent from the brain at 10 weeks of age

• total loss of brain hFA-galactolipids at 3 months of age

behavior/neurological

behavior/neurological phenotype ( J:171655 )

N • unlike germline null mice, no defects in learning are detected using a water T maze or a morris water maze

impaired coordination ( J:171655 )

• at 12 months of age

decreased vertical activity ( J:171655 )

• at 12 months of age

• reduction in vertical activity is more severe than that in horizontal activity

decreased locomotor activity ( J:171655 )

• decrease in spontaneous activity at 12 months of age

Genotype
MGI:3055718

cn8

• Allelic Composition: Gt(ROSA)26Sor^tm1(DTA)Riet/Gt(ROSA)26Sor⁺; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

postnatal lethality, complete penetrance ( J:92789 )

• double mutants die between P12 and P14

behavior/neurological

tremors ( J:92789 )

• double mutants develop tremors around P8-10

paraparesis ( J:92789 )

• double mutants develop hindlimb weakness around P8-10

growth/size/body

weight loss ( J:92789 )

• around P8-10 double mutants begin to lose weight

nervous system

absent oligodendrocytes ( J:92789 )

• from P0 to P14, no oligodendrocytes can be detected in double mutants

axon degeneration ( J:92789 )

• large clusters of unmyelinated axons that show signs of degeneration and are not surrounded by Schwann cells are seen

demyelination ( J:92789 )

• loss of oligodendrocytes and a subset of Schwann cells results in a dramatic decrease in the number of myelinated fibers in the nerves and large clusters of unmyelinated axons are seen

Genotype
MGI:3852096

cn9

• Allelic Composition: Myrf^tm1Barr/Myrf^tm1Barr; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6

mortality/aging

postnatal lethality, complete penetrance ( J:150563 )

• mice die during third postnatal week

behavior/neurological

tremors ( J:150563 )

• severe tremors are observed

seizures ( J:150563 )

• seizures develop postnatally

nervous system

seizures ( J:150563 )

• seizures develop postnatally

abnormal oligodendrocyte morphology ( J:150563 )

• 2-fold higher levels of apoptotic cells (having blebbed processes, fragmented nuclei) are observed in premyelinating oligodendrocytes compared to controls; transition from premyelinating to mature oligodendrocytes is blocked when assayed at P7

• postmitotic oligodendrocytes are generated but then undergo apoptosis

abnormal spinal cord morphology ( J:150563 )

• severe loss of myelin is observed in spinal cord at P16, but spinal roots are myelinated

abnormal myelination ( J:150563 )

• severe loss of myelination in CNS white matter tracts is observed at P16

Genotype
MGI:3653839

cn10

• Allelic Composition: Gt(ROSA)26Sor^tm2(DTA)Riet/Gt(ROSA)26Sor⁺; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

mortality/aging

postnatal lethality, complete penetrance ( J:110983 )

• double mutants die between P12 and P14

behavior/neurological

tremors ( J:110983 )

• double mutants develop tremors around P8-10

paraparesis ( J:110983 )

• double mutants develop hindlimb weakness around P8-10

growth/size/body

weight loss ( J:110983 )

• around P8-10 double mutants begin to lose weight

nervous system

absent oligodendrocytes ( J:110983 )

• from P0 to P14, no oligodendrocytes can be detected in double mutants

axon degeneration ( J:110983 )

• large clusters of unmyelinated axons that show signs of degeneration and are not surrounded by Schwann cells are seen

demyelination ( J:110983 )

• loss of oligodendrocytes and a subset of Schwann cells results in a dramatic decrease in the number of myelinated fibers in the nerves and large clusters of unmyelinated axons are seen

Genotype
MGI:3835562

cn11

• Allelic Composition: Erbb3^tm2Cbm/Erbb3^tm3Cbm; Erbb4^tm1Fej/Erbb4^tm1Fej; Cnp^tm1(cre)Kan/?
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

mortality/aging

postnatal lethality, complete penetrance ( J:145464 )

• develop to term but die in the second post natal week

nervous system

nervous system phenotype ( J:145464 )

N • central nervous system myelination is normal up to 11 days of age (optic nerve and corpus callosum)

abnormal myelination ( J:145464 )

• severely defective myelination in the peripheral nervous system

Genotype
MGI:3580007

cn12

• Allelic Composition: Fdft1^tm1Kan/Fdft1^tm1Kan; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ

mortality/aging

premature death ( J:98525 )

• about one-third of mutant mice died between 20 and 30 days

• mutants that survived past 1 month of age rarely died prematurely

nervous system

nervous system phenotype ( J:98525 )

N • homozygous mutant mice that are heterozygous for Cnp1^tm1(cre)Kan, in which cre mediated recombination is induced in oligodendrocyte and Schwann cells, were normal at birth

N • did not reveal any obvious oligodendrocytes loss, or apoptosis

demyelination ( J:98525 )

• severe dysmyelination of the spinal white matter which was almost of devoid of myelin at P20

• the corpus callosum and the cerebellar white matter also showed a marked reduction of myelin

• but no obvious ultrastructural defects in the myelin architecture was found

behavior/neurological

tremors ( J:98525 )

• starting at 2 weeks of age

• the trembling phenotype improved with age

ataxia ( J:98525 )

• starting at 2 weeks of age

impaired coordination ( J:98525 )

• the motor performance on rotarod testing was markedly lower

impaired limb coordination ( J:98525 )

• impaired control of hindlimb movements starting at 2 weeks of age

growth/size/body

postnatal growth retardation ( J:98525 )

• mutant mice lagged behind controls in weight gain

reproductive system

reduced fertility ( J:98525 )

• overall breeding performance was poor

Genotype
MGI:5431958

cn13

• Allelic Composition: Drp2^tm1.1Brp/Y; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

nervous system

nervous system phenotype ( J:185953 )

♂N • mice do not exhibit any functional defects in nerves

abnormal Schwann cell morphology ( J:185953 )

♂ • Cajal bands are disrupted

♂ • increased Schmidt-Lanterman incisures at 6 weeks

increased Schwann cell number ( J:185953 )

♂ • supernumerary

abnormal myelin sheath morphology ( J:185953 )

♂ • myelin outfoldings, focal hypermyelination and onion bulbs with thin myelin

♂ • defects increase with time

hypermyelination ( J:185953 )

♂ • focal

Genotype
MGI:4836647

cn14

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ

mortality/aging

premature death ( J:161841 )

digestive/alimentary system

megacolon ( J:161841 )

• mutants develop megacolon later in life

abnormal salivary gland morphology ( J:161841 )

• mutants develop hyperplasia of the salivary glands later in life

endocrine/exocrine glands

abnormal salivary gland morphology ( J:161841 )

• mutants develop hyperplasia of the salivary glands later in life

nervous system

increased brain size ( J:161841 )

abnormal brain white matter morphology ( J:161841 )

• increase in white matter volume

• progressive enlargement of all white matter tracts

abnormal corpus callosum morphology ( J:161841 )

• myelinated axons of the corpus callosum that intermingle with glial cells are in disarray

• density of myelinated axons in the ventral corpus callosum is decreased by 36.6% at 3 months of age

abnormal oligodendrocyte morphology ( J:161841 )

• oligodendroglial hypertrophy is seen at 4 months of age

abnormal Schwann cell morphology ( J:161841 )

• increase in numbers of myelinating and nonmyelinating Schwann cells

abnormal myelin sheath morphology ( J:161841 )

• increase in myelin sheath thickness

abnormal sciatic nerve morphology ( J:161841 )

• sciatic nerves are increased in size

• myelinated axons are more loosely spaced in sciatic nerves

• number of myelinated axons in the sciatic nerve is higher at 3 months of age; increase in myelination is primarily for small caliber axons

hypermyelination ( J:161841 )

• hypermyelination in both white and gray matter

• hypermyelination is primarily a consequence of additional membrane wraps and not by altered ultrastructure

• increase in myelin thickness is seen for axons of all calibers, however not all fibers are visibly hypermyelinated

• however, do not see ectopic myelination of CNS axons that normally are unmyelinated

• normally nonmyelinated C-fiber axons are spirally enwrapped by Remak Schwann cells; up to 10 membrane layers per axon are seen resulting in non compacted myelin

• Remak Schwann cells also ensheath bundles of collagen fibrils

• myelin outfoldings of variable length and aberrant myelin depositions are seen in the corpus callosum

vision/eye

cataract ( J:161841 )

• mutants develop cataracts later in life

reproductive system

reduced fertility ( J:161841 )

• poor breeding

Genotype
MGI:6360217

cn15

• Allelic Composition: Anln^{tm1c(EUCOMM)Wtsi}/Anln^{tm1c(EUCOMM)Wtsi}; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6N
• Cell Lines: EPD0545_1_C09

nervous system

nervous system phenotype ( J:272250 )

N • at 6 months of age, optic nerves show no alterations in myelin sheath thickness, percentage of myelinated axons, or frequency of degenerating/degenerated axons relative to those in controls mice

N • no axonopathy, astrogliosis or microgliosis is observed

tomacula ( J:272250 )

• at P75, mice exhibit numerous myelin outfoldings in the CNS (e.g. optic nerve)

• myelin outfoldings do not exhibit a pin-needle-like shape but represent large sheets of compacted multilayered membrane stacks that extend considerably away from the myelinated axon

abnormal myelination ( J:272250 )

• mice display disrupted assembly of septin filaments in CNS myelin

• abundance of all myelin septins (SEPT2, SEPT4, SEPT7,SEPT8) is strongly reduced in myelin purified from mutant brains

• abundance of the membrane phospholipid phosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P₂) is reduced in myelin purified from mutant brains

decreased nerve conduction velocity ( J:272250 )

• at 6 months of age, nerve conduction velocity in the spinal cord is reduced by 15.5%

• however, no nodal or paranodal abnormalities are observed

Genotype
MGI:7523331

cn16

• Allelic Composition: Septin2^{tm1c(EUCOMM)Wtsi}/Septin2^{tm1c(EUCOMM)Wtsi}; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129S1/Sv * 129S4/SvJaeSor * 129X1/SvJ * C57BL/6N
• Cell Lines: EPD0175_4_D03

nervous system

abnormal sciatic nerve morphology ( J:339068 )

• 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 sciatic nerve lysates of control mice

Genotype
MGI:5749838

cn17

• Allelic Composition: Cnp^tm1(cre)Kan/Cnp⁺; Tfam^tm1Lrsn/Tfam^tm1Lrsn
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

premature death ( J:228933 )

• most mice die by 12 weeks of age

nervous system

decreased neuron mitochondrial DNA content ( J:228933 )

abnormal enteric neuron morphology ( J:228933 )

• in the proximal and distal small intestine at 2 and 7 weeks

• however, the number of enteric neurons in the colon is not significantly different

abnormal PNS glial cell morphology ( J:228933 )

• in the proximal and distal small intestine at 2 and 7 weeks

• however, the number of glia in the colon is not significantly different

decreased neuron number ( J:228933 )

• loss of nitrergic inhibitory neuron

neurodegeneration ( J:228933 )

• profound in more proximal regions of the small intestine

axon degeneration ( J:228933 )

• of enteric neurons in proximal and distal small intestine

growth/size/body

decreased body size ( J:228933 )

• after 2 weeks of age

postnatal growth retardation ( J:228933 )

• after 2 weeks of age

distended abdomen ( J:228933 )

• at about 6 to 8 weeks of age

digestive/alimentary system

abnormal colon morphology ( J:228933 )

• small diameter colon

abnormal small intestine morphology ( J:228933 )

• massive dilation within the proximal small bowel with dark-colored luminal content and relative contraction of the distal small bowel with no stool pellets in the colon or rectum

• small diameter small intestine

• however, no stenosis or mechanical cause of the obstruction is evident

cellular

decreased mitochondrial DNA content ( J:228933 )

• in enteric neurons and glia

decreased neuron mitochondrial DNA content ( J:228933 )

Genotype
MGI:3851811

cn18

• Allelic Composition: Pex5^tm1Pec/Pex5^tm1Pec; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

premature death ( J:123503 )

• 91% are dead by 12 months of age

• none survive past 13 months

behavior/neurological

tremors ( J:123503 )

• hind limb tremors develop after 12 months

ataxia ( J:123503 )

• hind limb ataxia in about 14% of mice by 3 months of age

• symptoms most obvious after 9 months

hindlimb paralysis ( J:123503 )

• hind limb paralysis develops eventually

hindlimb paresis ( J:123503 )

• hind limb paresis develops over 12 months

nervous system

abnormal brain white matter morphology ( J:123503 )

• defects seen in rostral white matter by 4 months of age

• defects in the hippocampal commissure and cerebellar white matter less extensive

• defects become more extensive with time

• subcortical white matter degeneration increases as behavioral disorders progress

abnormal glial cell morphology ( J:123503 )

abnormal oligodendrocyte morphology ( J:123503 )

• defective peroxisomes in oligodendrocytes

gliosis ( J:123503 )

• massive gliosis in areas of demyelination

microgliosis ( J:123503 )

• activated microglia and macrophage appear early

abnormal axon morphology ( J:123503 )

• axonal swelling appears early in the corpus callosum and spinal cord

• gradual loss of myelinated nerve fibers

abnormal myelination ( J:123503 )

• very long chain fatty acids become progressively increased in myelin

respiratory system

abnormal breathing pattern ( J:123503 )

• difficulty breathing develops after 12 months

skeleton

kyphosis ( J:123503 )

• becomes prevalent in mice over 12 months of age

immune system

microgliosis ( J:123503 )

• activated microglia and macrophage appear early

abnormal inflammatory response ( J:123503 )

• infiltration of T cells into demyelinated regions of the brain by 4 months

• B cell infiltration sometimes seen as well

• proinflammatory proteins become more abundant

hematopoietic system

microgliosis ( J:123503 )

• activated microglia and macrophage appear early

Genotype
MGI:3836428

cn19

• Allelic Composition: Nfasc^tm1Bhat/Nfasc^tm1Bhat; Cnp^tm1(cre)Kan/?
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

mortality/aging

postnatal lethality, complete penetrance ( J:145846 )

• all homozygotes die before day 16 or 17

growth/size/body

weight loss ( J:145846 )

• progressive weight loss from 8 days of age onward

postnatal growth retardation ( J:145846 )

• size is normal until about 8 days of age

• noticeably smaller in stature by 12 days of age

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:145846 )

• progressive development of neurological disorders by 12 days of age

abnormal motor coordination/balance ( J:145846 )

impaired balance ( J:145846 )

• cannot maintain their balance on a stationary beam at 16 days of age

impaired coordination ( J:145846 )

• severe motor coordination defects at 16 days of age

abnormal limb posture ( J:145846 )

• day 16 mice hold their legs to the side and away from the body

decreased locomotor activity ( J:145846 )

• hypomobility at 16 days of age

• nearly immobile in open field tests

nervous system

abnormal axon morphology ( J:145846 )

• potassium channels become mislocated to the paranodal region adjacent to the normally distributed sodium channels

• abnormal association of paranodal loops with axons in the white matter of the spinal cord

• axonal accumulation of mitochondria and smooth endoplasmic reticulum

abnormal Purkinje cell axon morphology ( J:145846 )

• axonal swelling

• axonal degeneration

decreased nerve conduction velocity ( J:145846 )

• conduction velocity of tibial/plantar nerves is reduced about 50%

Genotype
MGI:4838222

cn20

• Allelic Composition: Nfasc^tm2Bhat/Nfasc^tm2Bhat; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

behavior/neurological

ataxia ( J:159621 )

impaired coordination ( J:159621 )

• motor coordination defects

growth/size/body

weight loss ( J:159621 )

• progressive weight loss after P13

nervous system

abnormal paranode morphology ( J:159621 )

• the formation of the distinct paranode domain in sciatic nerve fibers or in CNS myelinated fibers is perturbed with Caspr (Cntnap1) protein not remaining localized to the paranodal region and appearing diffused throughout the internode

• shaker-type potassium channels and Caspr2 (Cntnap2) protein are redistributed from the juxtaparanode to the paranodal space

• however, ankrynG and NF186 remain localized to the nodes, similar to controls

abnormal paranodal axoglial junction morphology ( J:159621 )

• loss of septae-like junctions, formed between the glial paranodal loops and the axon, is seen in the paranodal regions of the sciatic nerve, spinal cord white matter tracts and in Purkinje axons, with accumulation of organelles in the node

• in the CNS myelinated axons, the paranodal loops are often everted away from the axon, astrocytic processes infiltrate the paranodal space, and the parallel arrays of cytoskeletal neurofilaments are disrupted

Genotype
MGI:7523327

cn21

• Allelic Composition: Septin9^tm2.1Emfu/Septin9^tm2.1Emfu; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

nervous system

nervous system phenotype ( J:339068 )

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

Genotype
MGI:4429677

cn22

• Allelic Composition: Zfp24^tm1.1Pop/Zfp24^tm1.1Pop; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

behavior/neurological

tremors ( J:156938 )

• mild tremors at P14

tonic seizures ( J:156938 )

• at P14

nervous system

tonic seizures ( J:156938 )

• at P14

abnormal myelin sheath morphology ( J:156938 )

• spinal cord axons lack myelination

Genotype
MGI:5523949

cn23

• Allelic Composition: Hsd17b4^tm2Baes/Hsd17b4^tm2Baes; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

homeostasis/metabolism

increased fatty acids level ( J:201698 )

• accumulation of long chain fatty acids in the cerebellum

reproductive system

reproductive system phenotype ( J:201698 )

N • mice exhibit normal reproduction

behavior/neurological

behavior/neurological phenotype ( J:201698 )

N • mice exhibit normal coordination on a rotarod test at 6 and 12 months

growth/size/body

growth/size/body region phenotype ( J:201698 )

N • mice exhibit normal growth

nervous system

nervous system phenotype ( J:201698 )

N • mice exhibit normal myelination and cerebellum morphology

Genotype
MGI:6160757

cn24

• Allelic Composition: Plp1^{tm1c(EUCOMM)Wtsi}/Y; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6N

hematopoietic system

increased T cell number ( J:245100 )

♂ • density of T-lymphocytes (CD3+ cells) in the fimbria is increased at 26 weeks of age

microgliosis ( J:245100 )

♂ • microgliosis in the hippocampal fimbria at 26 weeks of age

immune system

increased T cell number ( J:245100 )

♂ • density of T-lymphocytes (CD3+ cells) in the fimbria is increased at 26 weeks of age

microgliosis ( J:245100 )

♂ • microgliosis in the hippocampal fimbria at 26 weeks of age

nervous system

microgliosis ( J:245100 )

♂ • microgliosis in the hippocampal fimbria at 26 weeks of age

abnormal hippocampal fimbria morphology ( J:245100 )

♂ • hippocampal fimbria exhibits APP+ axonal spheroids, microgliosis and astrogliosis, and increased density of T-lymphocytes

astrocytosis ( J:245100 )

♂ • moderate, but significant, astrogliosis in the hippocampal fimbria at 26 weeks of age

axonal spheroids ( J:245100 )

♂ • APP+ axonal spheroids are present in the hippocampal fimbria and corpus callosum at 26 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary spastic paraplegia 2		DOID:0110773	OMIM:312920	J:245100

Genotype
MGI:4820603

cn25

• Allelic Composition: Mtor^tm1Koz/Mtor^tm1Koz; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

nervous system

abnormal Schwann cell morphology ( J:181341 )

• mutant Schwann cells display arrested radial growth and reduced longitudinal growth

decreased Schwann cell number ( J:181341 )

• there is a 1.9-fold increase in the number of Schwann cells in mutant nerves compared with controls

abnormal axon morphology ( J:181341 )

• dramatic reduction in the cross-sectional area of peripheral mutant nerves which is first significant at P7 although these are not significantly different from controls until P21

abnormal axolemma morphology ( J:181341 )

• in unmyelinated, large diameter axons, in addition to some vacuolation and redundant basal lamina, the axonal membrane was highly irregular in outline

abnormal internode morphology ( J:181341 )

• internodes in mutant quadriceps nerves at P21 show a wider range of lengths compared with control nerves and mean values are reduced

abnormal myelin sheath morphology ( J:181341 )

• electron microscopy reveals that myelin is consistently thinner than normal; this aberrant ensheathment persists from P7 until P90; growth of the myelin sheath is retarded and/or arrested

• other derangements, such as myelin outfoldings, were also observed at low frequency in the mutant from P7 onwards but not in controls

abnormal myelination ( J:181341 )

• in P21 sciatic nerve lysates, there is a decrease in the amount of the major peripheral myelin protein P0, suggesting a deficit in myelin production

decreased nerve conduction velocity ( J:181341 )

• nerve conduction velocities of mutant nerves are severely reduced from 38.7 +/- 0.7 m/s to 11.7 +/- 1.5 m/s

behavior/neurological

abnormal motor coordination/balance ( J:181341 )

• poorer performance in the Rotarod test at P42; test was performed at two different speeds, 24 and 32 rpm

Genotype
MGI:6160760

cx26

• Allelic Composition: Plp1^tm1Kan/Y; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

hematopoietic system

increased T cell number ( J:245100 )

♂ • density of T-lymphocytes (CD3+ cells) in the fimbria is further increased at 26 weeks of age compared to single hemizygous Plp1 males

microgliosis ( J:245100 )

♂ • microgliosis in the hippocampal fimbria is further increased at 26 weeks of age compared to single hemizygous Plp1 males

immune system

increased T cell number ( J:245100 )

♂ • density of T-lymphocytes (CD3+ cells) in the fimbria is further increased at 26 weeks of age compared to single hemizygous Plp1 males

microgliosis ( J:245100 )

♂ • microgliosis in the hippocampal fimbria is further increased at 26 weeks of age compared to single hemizygous Plp1 males

nervous system

microgliosis ( J:245100 )

♂ • microgliosis in the hippocampal fimbria is further increased at 26 weeks of age compared to single hemizygous Plp1 males

abnormal hippocampal fimbria morphology ( J:245100 )

♂ • hippocampal fimbria exhibits APP+ axonal spheroids, microgliosis and astrogliosis, and increased density of T-lymphocytes

astrocytosis ( J:245100 )

♂ • moderate, but significant, astrogliosis in the hippocampal fimbria at 26 weeks of age

axonal spheroids ( J:245100 )

♂ • APP+ axonal spheroids are present in the hippocampal fimbria and corpus callosum at 26 weeks of age at enhanced levels compared to single hemizygous Plp1 males