Chapter 3 Biochemistry and Immunology of Neurological Mutants In The Mouse

Mallet, Jacques

doi:10.1016/s0070-2153(08)60116-7

Cited by 7 publications

(2 citation statements)

References 84 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Genetic mutations are convenient tools to obtain models of neuronal degeneration in mice (Sidman, 1968;Mallet, 1980). In particular, mutations leading to patterns of neuronal losses in the cerebellum have been studied extensively in the last two decades (Sotelo and Changeux, 1974;Mariani et al, 1977;Landis and Sidman, 1978;Caddy and Biscoe, 1979;Herrup and Mullen, 1979;Goffinet, 1984;Blatt and Eisenman, 1985;Shojaeian et al, 1985Shojaeian et al, , 1987Shojaeian et al, , 1988Shojaeian Zanjani et al, 1990;Heckroth et al, 1989).…”

mentioning

confidence: 99%

Evidence for a Hyperexcitability State of Staggerer Mutant Mice Macrophages

Kopmels

Mariani

Delhaye‐Bouchaud

et al. 1992

Journal of Neurochemistry

View full text Add to dashboard Cite

We recently reported an abnormal production of interleukin-1 (IL-1) in peripheral macrophages of several neurological mutant mice that exhibit patterns of neuronal degeneration, especially in the cerebellum. After in vitro activation by lipopolysaccharide acid (LPS), these macrophages hyperexpress IL-1 beta mRNA and hyperproduce IL-1 protein in comparison with +/+ controls. In the present study, focused on the staggerer mutant mice, we investigate if this genetic dysregulation is specific for IL-1 beta or if it reflects a generalized hyperexcitability of these macrophages. The hyperexpression of IL-1 beta mRNA in sg/sg macrophages is present whatever the duration of LPS stimulation, even for periods as short as 15 min, although it reaches a maximum after 4 h of stimulation. The hyperinducibility of sg/sg macrophages is observed even when very low doses of LPS are used (0.01 microgram/ml) and reaches its maximum for 5 micrograms/ml LPS. Synthetic molecules (muramyl dipeptides), such as N-acetylmuramyl-L-alanyl-D-isoglutamine or murabutide, known as macrophage activators, are also efficient in revealing the cytokine hyperexpression in sg/sg macrophages. In addition, hyperexpression of two other cytokines, i.e., tumor necrosis factor-alpha and IL-1 alpha mRNAs, is also detected in LPS-stimulated macrophages of mutant mice. Finally, the effect of an inhibitor of protein synthesis, cycloheximide, is similar in +/+ and sg/sg macrophages. As a whole, these data lead us to conclude that the sg/sg macrophages are in a state of general hyperexcitability when compared with +/+ ones.

show abstract

mentioning

confidence: 99%

Evidence for a Hyperexcitability State of Staggerer Mutant Mice Macrophages

Kopmels

Mariani

Delhaye‐Bouchaud

et al. 1992

Journal of Neurochemistry

View full text Add to dashboard Cite

show abstract

“…Those few examples prompted us to study potential IL-1 disorders in cases of neuronal degeneration of genetic origin in the mouse. In this species, several mutations are known t o produce neuronal degeneration of the cerebellum and of its afferent pathways (Sidman, 1968;Mallet, 1980). Especially one mutation aroused our interest, namely, the staggerer one.…”

mentioning

confidence: 99%

Interleukin‐1 Hyperproduction by In Vitro Activated Peripheral Macrophages from Cerebellar Mutant Mice

Kopmels

Wollman

Guastavino

et al. 1990

Journal of Neurochemistry

View full text Add to dashboard Cite

Several mutations in mice produce complex patterns of neuronal degeneration of the cerebellum and of its afferent pathways. In the staggerer (sg/sg) mutant, atrophy of the lymphoid organs and immunological abnormalities have been described. To search for a possible link between the neurological and the immune disorders in this mutant, we studied the production by its peripheral macrophages of interleukin-1 (IL-1), which roles in both immune and nervous systems are well established. Suspensions of peritoneal and/or spleen macrophages from mutants and their appropriate controls were stimulated in vitro by lipopolysaccharide. Northern and dot blots, performed with murine IL-1 cDNA probes, revealed a clear-cut hyperexpression of IL-1 mRNA in staggerer macrophages. An IL-1 bioassay using the IL-1-responsive D10.G4 cell line also revealed a sixfold increase of IL-1 activity in the macrophage supernatants of staggerer mutant mice. The hyperproduction was found in 3-week to 1-year-old staggerer and also in heterozygous (+/sg) mice. A similar phenomenon existed in cerebellar mutants lurcher, Purkinje cell degeneration (pcd), and to a lesser extent reeler and wobbler, but was absent in the neurological mutants weaver, jimpy, and motor end plate disease (medH). These observations establish that in several point mutations in mice, central nervous degeneration is associated with dysregulation of IL-1 production by peripheral macrophages.

show abstract

Spastic Mutant axolotl: Identification of a phenocopy pathway with implications for the control of axolotl swimming by the vestibulocerebellum

O¹,

Ide²,

Duda³

et al. 1983

J of Comparative Neurology

View full text Add to dashboard Cite

The spastic mutant axolotl shows abnormal swimming behavior, which includes a preponderance of "embryonic" swimming elements (coils) versus mature swimming elements (sinusoids) and a failure to entrain sinusoids into a prolonged swimming sequence. The mutant also shows anatomical disorganization in the area acousticolateralis and cerebellar auricle, but it is unclear (1) to what extent the behavioral abnormalities are traceable to the vestibulocerebellar defect or (2) how the vestibulocerebellar pathway modulates swimming behavior in the normal axolotl. We have performed quantitative cine analysis of electric shock-induced swimming bouts in normal axolotls, spastic mutants, and a variety of neurosurgically altered wild-type axolotls. We scored the incidence of coil elements (25% in controls, 70-90% in spastics) versus sinusoid elements, as well as length distributions of coilfree intervals (short to long trains of sinusoidal swimming) and of sinusoidfree intervals (of brief of prolonged coiling). We found that bilateral VIIIth nerve lesions or surgical undercutting of the cerebellar auricle in wild-type axolotls almost exactly reproduced the behavioral deficit seen in spastic (75-81% coils, loss of long sinusoid trains, and appearance of prolonged coiling intervals at least some of which coupled several coils into trains of thrashing behavior). By contrast, neither complete transection of the CNS at low midbrain levels nor section of cranial nerves V, VII, or X (lateral line) resulted in an increased incidence of coil elements beyond 26% nor significantly altered the length distributions of S-intervals and C-intervals. Nor did any of the latter lesions disrupt the spasticlike swimming patterns of axolotls already subjected to auricle or VIIIth nerve lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Chapter 3 Biochemistry and Immunology of Neurological Mutants In The Mouse

Cited by 7 publications

References 84 publications

Evidence for a Hyperexcitability State of Staggerer Mutant Mice Macrophages

Evidence for a Hyperexcitability State of Staggerer Mutant Mice Macrophages

Interleukin‐1 Hyperproduction by In Vitro Activated Peripheral Macrophages from Cerebellar Mutant Mice

Spastic Mutant axolotl: Identification of a phenocopy pathway with implications for the control of axolotl swimming by the vestibulocerebellum

Contact Info

Product

Resources

About