‘Wasted’, a new mutant of the mouse with abnormalities characteristic of ataxia telangiectasia

Shultz, L D; Sweet, Hope O.; Davisson, Muriel T.; Coman, Dale Rex

doi:10.1038/297402a0

Cited by 92 publications

(62 citation statements)

References 7 publications

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“…In 1982, Shultz et al (63) described the wasted mouse with a spontaneous autosomal recessive defect that gives rise to a set of abnormalities. These include muscle wasting (hence the name of the mutation), weight loss, progressive paralysis, and neural degeneration.…”

Section: Ef1␣2 Expression In Dcs In Relation To the Wasted Mouse Phenmentioning

confidence: 99%

T Cell Tolerance Based on Avidity Thresholds Rather Than Complete Deletion Allows Maintenance of Maximal Repertoire Diversity

Sandberg

Franksson

Sundbäck

et al. 2000

The Journal of Immunology

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Given the flexible nature of TCR specificity, deletion or permanent disabling of all T cells with the capacity to recognize self peptides would severely limit the diversity of the repertoire and the capacity to recognize foreign Ags. To address this, we have investigated the patterns of CD8+ CTL reactivity to a naturally H-2Kb-presented self peptide derived from the elongation factor 1α (EF1α). EF1α occurs as two differentially expressed isoforms differing at one position of the relevant peptide. Low avidity CTLs could be raised against both variants of the EF1α peptide. These CTLs required 100-fold more peptide-H-2Kb complexes on the target cell compared with CTLs against a viral peptide, and did not recognize the naturally expressed levels of EF1α peptides. Thus, low avidity T cells specific for these self peptides escape tolerance by deletion, despite expression of both EF1α isoforms in dendritic cells known to mediate negative selection in the thymus. The low avidity in CTL recognition of these peptides correlated with low TCR affinity. However, self peptide-specific CTLs expressed elevated levels of CD8. Furthermore, CTLs generated against altered self peptide variants displayed intermediate avidity, indicating cross-reactivity in induction of tolerance. We interpret these data, together with results previously published by others, in an avidity pit model based on avidity thresholds for maintenance of both maximal diversity and optimal self tolerance in the CD8+ T cell repertoire.

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Section: Ef1␣2 Expression In Dcs In Relation To the Wasted Mouse Phenmentioning

confidence: 99%

T Cell Tolerance Based on Avidity Thresholds Rather Than Complete Deletion Allows Maintenance of Maximal Repertoire Diversity

Sandberg

Franksson

Sundbäck

et al. 2000

The Journal of Immunology

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“…Mice develop a rapid neurodegeneration and die around P28. Finally, several studies demonstrated that this model bears increased chromosomal breakage and DNA damage (Shultz et al, 1982).…”

Section: Wasted Mousementioning

confidence: 99%

Advantages and Pitfalls in Experimental Models Of ALS

Boido¹,

Buschini²,

Piras³

et al. 2012

Amyotrophic Lateral Sclerosis

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“…The mouse develops tremors, ataxia, and progressive paralysis at postnatal day 21 (P21) and dies by P28 [9]. During this postweaning period, wasted mice also develop progressive atrophy of the spleen and thymus [14]. Originally, wasted mice were proposed as a murine model for ataxia telangiectasia [14], but further studies did not find a strong relationship between this model and ataxia telangiectasia.…”

Section: Introductionmentioning

confidence: 99%

“…During this postweaning period, wasted mice also develop progressive atrophy of the spleen and thymus [14]. Originally, wasted mice were proposed as a murine model for ataxia telangiectasia [14], but further studies did not find a strong relationship between this model and ataxia telangiectasia. Previous morphological study reported that wasted mice showed prominent vacuolar degeneration within anterior horns of the spinal cord and motor nuclei of the brainstem without abnormalities in Purkinje cells [9].…”

Section: Introductionmentioning

confidence: 99%

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Nuclear Envelope Breakdown Is a Prominent Feature in Spinal Motor Neurons of Wasted Mice

Ueda

Tezuka

Nakamura

2004

Acta Histochem. Cytochem

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It has been thought that the wasted mouse is a good model for motor neuron disease. Recently, it was found that the wasted mouse is caused by a gene defect of elongation factor 1a2, but the mechanism of the abnormal phenotype remains poorly understood. In the present study, we examined spinal motor neurons of wasted mice with light and electron microscopy. Confocal images with lamin B immunolabeling and conventional electron micrographs demonstrate that nuclear envelope breakdown (NEB) is a prominent feature of large motor neurons in wasted mice, although probable intercalated neurons or glial cells show no abnormalities. Furthermore, motor neuron death in wasted mice seems to be neither apoptosis nor necrosis. These data suggest that to understand the mechanism about NEB of the spinal motor neuron in wasted mice could shed light on certain motor neuron diseases.

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‘Wasted’, a new mutant of the mouse with abnormalities characteristic of ataxia telangiectasia

Cited by 92 publications

References 7 publications

T Cell Tolerance Based on Avidity Thresholds Rather Than Complete Deletion Allows Maintenance of Maximal Repertoire Diversity

T Cell Tolerance Based on Avidity Thresholds Rather Than Complete Deletion Allows Maintenance of Maximal Repertoire Diversity

Advantages and Pitfalls in Experimental Models Of ALS

Nuclear Envelope Breakdown Is a Prominent Feature in Spinal Motor Neurons of Wasted Mice

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