Shiverer*jimpy double mutant mice. II. Morphological evidence supports reciprocal intergenic suppression

Billings‐Gagliardi, Susan; Wolf, Merrill K.; Kirschner, Daniel A.; Kerner, Ann-Louise

doi:10.1016/0006-8993(86)90394-x

Cited by 21 publications

(6 citation statements)

References 17 publications

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“…Since the double mutant animals can survive at least 20-21 days, this directly demonstrates that theshi/shi*jp/Y genotype is not lethal in útero. This result strengthens our previous morpho logical studies conducted on mice bred from the same B6C3Fi-derived stocks and identified by the same crite ria [28].…”

Section: Discussionsupporting

confidence: 89%

“…In the quaking*jimpy double mutant (qk/qk*jp/Y), there is virtually no PLP protein, like j p / Y alone, but there are many more myelinated axons, suggesting partial suppression of the jp defect in oligodendrocyte survival [29]. In shi/shi*jp/Y too, the amount of PLP is below the detectable range, yet our previous morphological studies suggest a larger number of oligodendrocytes than in jp alone [28,30], This new result therefore is consistent with the idea that when jp is combined with another myelin mutation at least two effects of the PLP mutation -on PLP levels and on oligodendrocyte survival -can be independently regu lated.…”

Section: Discussionmentioning

confidence: 90%

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Shiverer*jimpy Double Mutant Mice

et al. 1991

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We have reexamined the levels of myelin basic protein (MBP) and proteolipid protein (PLP) in the brains of mice bred to carry both the shi/shi and jp/Y hypomyelination defects. The genotype of each putative double mutant was confirmed by direct DNA analysis: shi/shi by Southern blot analysis, and jp/Y by restriction enzyme analysis of polymerase chain reaction-amplified fragments. MBP and PLP levels were assessed by immunoblotting. All putative double mutants were found to be shi/shi. However, examination of the PLP locus revealed both jp and wild-type genotypes, the latter produced by an expected crossover. Animals proven to be shi/shi*jp/Y hadno detectable MBP or PLP; those proven to be shi/shi*+/Y (the crossover) had no MBP but had PLP. These results differ from an earlier report of both MBP and PLP in the brains of presumed shi*jp animals.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 90%

Shiverer*jimpy Double Mutant Mice

et al. 1991

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“…The finding that shortened life span cannot be related to the amount of CNS myelination is supported by previous observations that the double mutant shiverer * jimpy dies at the same time as jimpy alone, but has a larger amount of myelin than is seen in homozygous shi [18][19][20]. In addition, shi mice which are also heterozygous for the MBP 1 transgene have much more myelin than mice that express just shi [21], yet they usually die at 4-5 months, just like shi.…”

Section: No Causal Relationship Exists Between Life Span and Extent Osupporting

confidence: 66%

Quaking*Shiverer Double-Mutant Mice Survive for at Least 100 Days with No CNS Myelin

Wolf¹,

Nunnari²,

Billings‐Gagliardi³

1999

Dev Neurosci

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Mice expressing mutations that produce CNS hypomyelination often die prematurely: the more severe the hypomyelination, the shorter the life span. However, we have previously described jimpy-msd mice that survive twice as long as usual; although they acquire significantly increased amounts of myelin, they still succumb long before their unaffected littermates. This result contradicts any postulated causal relationship between extent of CNS hypomyelination and premature death of the animal. Here we have addressed this question in another way, by using an animal model that does not involve a proteolipid protein (Plp) gene mutation. We demonstrate that quaking*shiverer double-mutant mice can survive for at least 100 days without any CNS myelin whatsoever. Therefore, at least for a mouse, absence of CNS myelin is not lethal per se.

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“…Unexpectedly, we found that in shi*jp double mutant mice, the shi mutation can suppress many jp features including reduction of OL numbers, and that the double mutant phenotype was morphologically similar to shi [17,18]. The shi and jp-msd mutations each suppress some features of the other, and the double mutant looked 'intermediate' with respect to effects on the morphologic phenotype.…”

Section: Introductionmentioning

confidence: 83%

Rumpshaker Behaves like Juvenile-Lethal Plp Mutations When Combined with Shiverer in Double Mutant Mice

Billings‐Gagliardi¹,

Nunnari²,

Wolf³

2001

Dev Neurosci

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The phenotypes of double mutant mice whose genomes are homozygous for an Mbp (myelin basic protein) mutation and hemizygous for a juvenile-lethal Plp (proteolipid protein) mutation were compared in earlier studies. The results suggested that the shiverer Mpb mutation might have some unexplained ability to partially rescue oligodendrocytes (OLs) from the ‘death sentence’ that is imposed by the Plp mutations. Conversely, they also indicated that the juvenile-lethal Plp mutations may normalize shiverer OL morphology by reducing the numbers of microprocesses. The Plp mutation rumpshaker produces a mild hypomyelination without reduction in OL numbers and a normal lifespan. This report describes double mutant mice combining two Mbp mutations with rumpshaker, utilizing a common B6C3F1 hybrid-based genetic background. Initial studies on B6C3F1 rumpshaker optic nerve and spinal cord white matter showed unanticipated signs of OL death, with morphologic criteria suggestive of an apoptotic mechanism. In shiverer*rumpshaker double mutant mice, this small class of dying cells could not be identified. White matter morphology was similar to that of mice expressing only the shiverer mutation, except that OL microprocesses were far less abundant. This evidence suggests that, despite their distinctive phenotypic differences, rumpshaker may share more characteristics with the juvenile-lethal Plp mutations than has previously been recognized.

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Shiverer*jimpy double mutant mice. II. Morphological evidence supports reciprocal intergenic suppression

Cited by 21 publications

References 17 publications

<i>Shiverer*jimpy </i>Double Mutant Mice

<i>Shiverer*jimpy </i>Double Mutant Mice

Quaking*Shiverer Double-Mutant Mice Survive for at Least 100 Days with No CNS Myelin

Rumpshaker Behaves like Juvenile-Lethal <i>Plp</i> Mutations When Combined with Shiverer in Double Mutant Mice

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