Mbpshi
Spontaneous Allele Detail
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| Nomenclature |
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Symbol:
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Mbpshi
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Name:
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myelin basic protein;
shiverer
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MGI ID: |
MGI:1856159 |
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Synonyms: |
shi |
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Gene:
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Mbp
Location:
Chr18:82644538-82755029 bp, + strand
Genetic Position: Chr18,
55.0 cM, cytoband E2-E4
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The Mbpshi/Mbpshi mouse
Show the 1 image(s) involving this allele.
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Mutation
origin |
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Mutation
description |
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Allele
Type: |
Spontaneous |
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Mutation: |
Intragenic deletion |
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The shiverer mutation involves a large deletion from intron 1 to exon 6. The portion of the gene remaining includes exon 1 and 12.4-14.4 kb of intron 1 sequences. (J:7925, J:7748, J:20098, J:78561) |
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Inheritance: |
Recessive |
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| Find Mice (IMSR) |
Mouse strains and cell lines available from the
International Mouse Strain Resource
(IMSR)
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Phenotype
summary
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Phenotype Summary by Mammalian Phenotype terms
(show or
hide all annotated terms)
Genotypes are listed in the next section.
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Key:
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| hm |
homozygous |
ht |
heterozygous |
| cn |
conditional genotype |
cx |
complex: > 1 genome feature |
| tg |
involves transgenes |
ot |
other: hemizygous, indeterminate,... |
| N |
normal phenotype |
 |
expected model not found |
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Phenotypic
data by
genotype
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Phenotypic Data by Genotype
(show or
hide all phenotypic details)
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Notes |
This mutation arose in the Swiss Vancover (SWV) stock at the University of British Columbia. From 12 days of age, homozygotes show a generalized tremor during locomotion. This shivering increases in severity with age, and there is incoordination of the hindlimbs. Post-weaning mice undergo seizure-like attacks during which they may lie rigid and motionless for many seconds. Homozygotes are noticeably smaller than their littermates by 4 weeks of age and their life span is shortened. They usually die between 50 and 100 days of age, often while undergoing an attack. They are fertile but do not breed well (J:6578). There is a severe myelin deficiency throughout the CNS (J:20541), and a moderate hypomyelination in the PNS (J:7591). Occasional regions of normal appearing myelin are found throughout the CNS (J:6454). Most of the sparse myelin that forms in the CNS lacks the major dense line; in the PNS the major dense line is present (J:6179). Immunochemical studies have shown a lack of MBP in both CNS (J:6180) and PNS (J:6244, J:26640).
As noted above, there is a deletion of five of the six wild-type exons in the Mbpshi gene (J:7925). Transcription rates of the intact 5' end of the mutant gene follow the normal curve from 7 to 18 days of age; total transcripts follow a similar profile, but at about 5% of the normal level (J:2025).
Heterozygous (Mbpshi/+) mice behave normally and have structurally normal myelin but produce only half the normal amount of MBP in both CNS and PNS (J:7096, J:11954, J:7388). Translation products of polyribosomes isolated from brains of Mbpshi/Mbpshi and Mbpshi/+ mice produced 0% and 50% of control (+/+) amounts of MBP, respectively (J:7310). Co-culture experiments have shown that the effect of Mbpshi is intrinsic to the oligodendrocytes, which produce CNS myelin sheaths, and the Schwann cells that perform this function in the PNS (J:7423, J:7414).
The insertion of a transgenic Mbp gene into Mbpshi mice, which restores 25% of normal MBP levels and corrects shivering and premature death, also improves interpeak latency in brain-stem auditory potentials (J:19586). Oligodendrocytes from a normal embryonic mouse spinal cord, grafted into adult Mbpshi homozygotes, migrated to the site of naked axons and remyelinated them (J:27488). Migration and differentiation of transplanted oligodendrocytes has been traced (J:857).
Both shiverer and quaking mice show higher than normal levels of iron in oligodendrocytes and myelin sheaths in brain (J:1932). Oligodendrocyte transferrin is decreased in brain in Mbpshi/Mbpshi mice, although transferrin transcript levels are normal. Transferrin production in brain of these mice is correlated with the amount of myelin present, and regulated at the level of translation (J:16337). The acceleration of Schwann cell proliferation during nerve regeneration is normal in shiverer mice; MBP is not the myelin component responsible for this acceleration (J:74). Levels of Na+K+-ATPase do not differ between brains of shiverer and normal mice (J:27479). Decreased myelin-associated glycoprotein deposition does, however, occur in these animals (J:27478). Hypomyelinated axons show an elevated expression of type II Na+ channels in shiverer mice (J:1153). Mice deficient for both MBP and the peripheral myelin protein P0, encoded by the Mpz gene, lack the major dense line. Both proteins contribute to the formation of this line (J:26097). Double mutants for shiverer and the PLP- deficient mutation jimpy lacked both MBP and PLP; mice with PLP in the brain were shown to carry a + allele at the Plp1 locus (J:2529). Brain levels of cholesterol, a component of myelin, and of cholesterol metabolites, are reduced in shiverer and quaking mutants, but not in the trembler mutation of the Pmp22 peripheral myelin protein gene (J:9907).
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| References |
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Original: |
J:6578
Chernoff GF,
"Shiverer: an autosomal recessive mutant mouse with myelin deficiency."
J Hered 1981 Mar-Apr;72(2):128
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All: |
86 reference(s)
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