Phenotypes associated with this allele

• Allele Symbol: Mpz^tm3.1Wra
• Allele Name: targeted mutation 3.1, San Raffaele Scientific Institute
• Allele ID: MGI:5909317
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Mpz^tm3.1Wra/Mpz^tm3.1Wra	FVB.129S2(Cg)-Mpz^tm1.1Wra	MGI:6191698
ht2	Mpz^tm3.1Wra/Mpz^+	FVB.129S2(Cg)-Mpz^tm3.1Wra	MGI:6191699
cx3	Ddit3^tm1Dron/Ddit3^tm1Dron Mpz^tm3.1Wra/Mpz^tm3.1Wra	involves: 129S2/SvPas * C3H * C57BL/6 * FVB/N	MGI:6191700

Genotype
MGI:6191698

hm1

• Allelic Composition: Mpz^tm3.1Wra/Mpz^tm3.1Wra
• Genetic Background: FVB.129S2(Cg)-Mpz^tm1.1Wra

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

behavior/neurological

tremors ( J:241742 )

• mice exhibit a persistent tremor that is exacerbated during walking

ataxia ( J:241742 )

• slow, unsteady gait apparent by time of weaning at about 21 days of age

impaired coordination ( J:241742 )

• mice are unable to maintain balance on the rotating rod

cellular

increased Schwann cell proliferation ( J:241742 )

• Schwann cell proliferation is increased in sciatic nerves

• however, no differences in Schwann cell apoptosis are seen

increased endoplasmic reticulum stress ( J:241742 )

• marker analysis indicates endoplasmic reticulum stress

nervous system

increased Schwann cell proliferation ( J:241742 )

• Schwann cell proliferation is increased in sciatic nerves

• however, no differences in Schwann cell apoptosis are seen

abnormal Schwann cell morphology ( J:241742 )

• marker analysis indicates that Schwann cell development is impaired and that cells are arrested in the promyelinating stage

abnormal myelin sheath morphology ( J:241742 )

• 9% increase in sciatic nerve myelin period; the wider period is accounted for by an approximate 20 angstrom swelling at the extracellular apposition

• however, optic nerve myelin period is normal

• sciatic nerve segments have a coherence length of myelin reduced by about 60% and a period distortion that is twice as much as in wild-type, indicating more membrane packing irregularity

decreased myelin sheath thickness ( J:241742 )

• sciatic nerves exhibit very thin and poorly compacted myelin when it is present at all at 6 weeks of age

abnormal sciatic nerve morphology ( J:241742 )

• the number of myelinated axons is reduced in sciatic nerves

dysmyelination ( J:241742 )

• virtually no myelin is present in P2 mice, suggesting that myelination is delayed

• myelin abnormalities are similar at 2 weeks, 6 weeks, and 9 months of age, indicating no progression of myelin abnormalities after 2 weeks

• small diameter axons are less affected than large diameter axons

abnormal action potential ( J:241742 )

• evoked compound muscle action potential amplitudes are reduced

decreased nerve conduction velocity ( J:241742 )

• mice have severely slowed nerve conduction velocities at 6-8 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Charcot-Marie-Tooth disease type 1B		DOID:0110152	OMIM:118200	J:241742

Genotype
MGI:6191699

ht2

• Allelic Composition: Mpz^tm3.1Wra/Mpz⁺
• Genetic Background: FVB.129S2(Cg)-Mpz^tm3.1Wra

behavior/neurological

impaired coordination ( J:241742 )

• mice perform worse than wild-type mice on the rotating rod

cellular

increased Schwann cell proliferation ( J:241742 )

• Schwann cell proliferation is increased in sciatic nerves

• however, no differences in Schwann cell apoptosis are seen

nervous system

increased Schwann cell proliferation ( J:241742 )

• Schwann cell proliferation is increased in sciatic nerves

• however, no differences in Schwann cell apoptosis are seen

abnormal Schwann cell morphology ( J:241742 )

• Schwann cell development is delayed

abnormal myelin sheath morphology ( J:241742 )

• about 1% increase in sciatic nerve myelin period

• however, optic nerve myelin period is normal

• sciatic nerve segments have a coherence length of myelin reduced by about 30% and a period distortion that is about 25% greater, indicating more membrane packing irregularity

decreased myelin sheath thickness ( J:241742 )

• sciatic nerves show thinner myelin and an increased average G-ratio of 0.77 compared to 0.67 in wild-type controls at 6 weeks of age

• small diameter axons are less affected than large diameter axons

abnormal sciatic nerve morphology ( J:241742 )

• the number of myelinated axons is reduced in sciatic nerves

abnormal action potential ( J:241742 )

• evoked compound muscle action potential amplitudes are reduced but to a lesser extent than in homozygotes

decreased nerve conduction velocity ( J:241742 )

• mice have slowed nerve conduction velocities at 6-8 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Charcot-Marie-Tooth disease type 1B		DOID:0110152	OMIM:118200	J:241742

Genotype
MGI:6191700

cx3

• Allelic Composition: Ddit3^tm1Dron/Ddit3^tm1Dron; Mpz^tm3.1Wra/Mpz^tm3.1Wra
• Genetic Background: involves: 129S2/SvPas * C3H * C57BL/6 * FVB/N

behavior/neurological

impaired coordination ( J:241742 )

• mice show no improvement in rotarod function, with nice unable to retain balance on the rotarod

nervous system

decreased myelin sheath thickness ( J:241742 )

• mice show no morphological changes in myelin, showing very thin, if any, myelin in sciatic nerves

dysmyelination ( J:241742 )

• mice show no improvement in myelination

decreased nerve conduction velocity ( J:241742 )

• mice show no changes in nerve conduction velocities, showing severely slowed nerve conduction velocities at 6-8 weeks of age