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At least 19 recordsLinked to original sources
PubMed1988

A survey of neurological mutant mice. II. Lipid composition of myelinated tissue in possible myelin mutants.

The lipids of white matter and peripheral nerve from neurological mutant mice with possible myelin abnormalities were analyzed by thin-layer chromatography and quantitated by densitometry. Eight mutants had major abnormalities in the central nervous system (CNS) and/or peripheral nervous system (PNS) tissues examined (optic nerve, and trigeminal and sciatic nerves). In the optic nerve of axJ/axJ, there were increases of 20-30% in the levels of the major phospholipids; peripheral nerve was normal. In bc3J/bc3J CNS, the major phospholipids and cholesterol were increased by 25-40%; the PNS was normal. In myd/myd CNS, there were increases of about 20% in the levels of both forms of cerebrosides and in the major phospholipids; in the PNS the lipids were normal. ot/ot CNS had 20-40% reductions of all the glycolipids and minor alterations in some of the phospholipids and cholesterol; the PNS had 20% losses of both forms of cerebrosides. In the PNS of ji/ji, there were decreases of 10-40% among the glycolipids and of 15-25% in three of the major phospholipids; the CNS was virtually normal. In the PNS of dtJ/dtJ, vb/vb and wr/wr, almost all lipids were significantly decreased. The CNS of dtJ/dtJ and vb/vb were normal; wr/wr had minor reductions of certain glycolipids and phospholipids. Six mutants had relatively minor lipid abnormalities in their myelinated tissues. In cr/cr PNS, there were elevated levels of the cerebrosides and major phospholipids; the CNS was virtually normal. In db/db CNS and PNS, there were reduced levels of the nonhydroxy forms of cerebroside and sulfatide. The major change in htr/htr was the elevation of all the glycolipids in the CNS. In the CNS of Lc/+, nonhydroxy cerebroside was reduced. In shm/shm PNS, nonhydroxy sulfatide was elevated and there were small decreases in some of the phospholipids. wl/wl CNS showed decreases among most of the glycolipids. Mutants homozygous for du, mto, spa and tg had virtually normal lipid levels in both the optic and peripheral nerves. Cholesterol ester, lysophospholipids and other unusual lipid species were not detected in any of the mutants. The plasmalogen forms of ethanolamine and choline phosphatides were at normal levels in all mutants that otherwise had significant alterations among their lipids. Although many alterations in lipid composition were found in these mutants, the changes were moderate compared to the classical myelin mutants and indicate that none of the mutants are severely myelin-deficient.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1980

Brain nucleic acids and protein in various neurological mutant mice.

A study was made to compare alterations in the cerebral contents of nucleic acids and protein of several mouse strains affected by different neurological mutations: jimpy, msd, quaking, reeler, weaver, and dwarf. In normal and affected jimpy and msd mice the brain components analyzed were very similar. On the other hand, the cerebral hemispheres of quaking mice showed significant decreases in total RNA and DNA, when compared with those of normal littermates. In the affected reeler and weaver mice, total protein, RNA, and DNA in the cerebellum differed markedly from controls. Protein decreased slightly, whereas nucleic acids showed no significant variation in the cerebral hemispheres of the same mutants. The cerebella and cerebral hemispheres of affected dwarf mice had wet weights and total protein contents that were about 20% lower than those of their controls; DNA did not vary significantly in the various brain regions analyzed. The decrease of DNA we report in reeler and weaver mutant cerebellum in toto quantifies the lack of cell number, in contrast to histological studies which give only semiquantitative information.

Animals↗
PubMed1982

Alterations in Clarke's column secondary to granule cell degeneration in the neurological mutant mice, weaver and staggerer.

In the neurological mutants weaver and staggerer, the granule cells either do not successfully migrate into the granular (weaver) or, having migrated, die during the second postnatal week (staggerer). We wished to determine if the resulting agranular cortex might produce retrograde transneuronal changes in the spinal cord similar to the changes observed after neonatal hemicerebellectomy. Golgi analysis of Clarke's column indicates that neurons in weaver are affected; neurons in staggerer are not. These observations support the view that neuronal maturation requires the presence of a target nucleus during "critical' postnatal growth periods.

Afferent Pathways↗
PubMed1982

Radial component of the central myelin in neurologic mutant mice.

The radial component of central myelin, a series of radially oriented interlamellar tight junctions, was investigated in three neurologic mutant mice with myelin disorders--quaking, jimpy, and twitcher. In normal adult mice, the radial component of compacted myelin sheaths was usually localized deep in the myelin sheath lying under the cytoplasm of oligodendroglia, in particular between outer and inner tongues. In quaking mice, there were numerous rows of interlamellar tight junctions in the compacted myelin sheaths, and a single tight junction was frequently found between the opposing plasma membranes of oligodendroglia. The junctions were usually closely associated with cytoplasmic islands of oligodendroglia, but redundant myelin sheaths without associated axons or islands of oligodendroglia also occasionally revealed numerous radial components or rows of interlamellar tight junctions. In jimpy mice, the radial component was very poorly developed and could not be detected in the majority of myelin sheaths. Rare radial components were usually extended only partially across the myelin sheaths. In contrast to quaking and jimpy mice, the pattern and distribution of the radial component in twitcher mice were identical in the preclinical stage to that of the normal mouse. These observations further suggest that myelination is abnormal in quaking and jimpy mice but not in the twitcher mouse.

Animals↗
PubMed1988

A survey of neurological mutant mice. I. Lipid composition of myelinated tissue in known myelin mutants.

The lipids of white matter and peripheral nerve from mutant mice with known myelin deficiencies were analyzed by one- and two-dimensional high-performance thin-layer chromatography and quantitated by densitometry. In optic nerve, the mutants jp/Y, jpmsd/Y, qk/qk, shi/shi and shimld/shimld, which have severe central nervous system (CNS) myelin deficiency, had a common pattern of lipid loss: cerebrosides and sulfatides (hydroxy and nonhydroxy forms) were generally reduced by 70-95% or more; most phospholipids were diminished by 15-55%, and cholesterol was reduced by 35-60%. Only in the CNS of jp/Y and jpmsd/Y did cholesterol ester accumulate. In peripheral nerve, the lipid composition varied markedly among these mutants. In jp/Y there was no change, while in jpmsd/Y there was a 5-15% loss among the phospholipids and cholesterol. Homozygous qk had reductions of 75-85% in the nonhydroxy forms of cerebroside and sulfatide, a 130% increase in hydroxy sulfatide, and a 55% loss of sphingomyelin. In shi/shi and shimld/shimld homozygotes, the glycolipids were altered by +/- 20%, most phospholipids and cholesterol were reduced by 5-15%, and sphingomyelin was reduced by 40%. Tr and TrJ showed 35-90% reductions in most lipid classes of the peripheral nervous system; CNS lipid composition was normal. Homozygous twi had a uniform loss of most lipid classes in both optic (generally 10-20%) and trigeminal nerves (generally 40-55%); cerebrosides did not accumulate in these tissues. dy/dy had a 10-20% reduction of cerebrosides in trigeminal nerve trunk. The CNS of dy homozygotes had 10-35% increases in specific classes of glycolipids and phospholipids, and in cholesterol. None of the mutants showed detectable levels of lysophospholipids or other unusual lipid species. The fractions of ethanolamine and choline phosphatides in the plasmalogen form were close to normal in all mutants.

Animals↗
PubMed1983

Fatty acid activation in the brains of neurologically mutant mice.

1. Palmitoyl-CoA synthetase activity was assayed in subfractions of control and Quaking, Jimpy, Shiverer and Trembler mouse brain. 2. Mouse brain palmitoyl-CoA synthetase activity is not altered during myelination. 3. Mouse brain enzyme activity (homogenate 1.5 +/- 0.3 nmol palmitoyl carnitine/min/per mg protein crude mitochondria 0.6 +/- 0.1 nmol/min/per mg protein and microsomes 1.9 +/- 0.3 nmol/min/per mg protein) does not differ markedly from rat and rabbit brain activity. 4. The lesions of the above mutants which affect myelination and lipid synthesis do not include the enzyme palmitoyl-CoA synthetase.

Animals↗
PubMed1992

Expression of c-kit, a proto-oncogene of the murine W locus, in cerebella of normal and neurological mutant mice: immunohistochemical and in situ hybridization analysis.

The c-kit proto-oncogene encodes a receptor tyrosine kinase and is allelic with the murine white-spoting (W) locus. Although no apparent defects in the brain have been reported in W mutant mice, brain tissue, especially cerebellum, shows a high level of c-kit transcription. In the present study, sites of c-kit expression in the cerebellum were exained by immunohistochemical and in situ hybridization techniques. Immunohistochemistry with a monoclonal antibody against c-Kit protein revealed that the c-Kit protein was localized close to the Purkinje cell soma in the region facing the granular cell layer. Similar distribution of the c-Kit protein was observed in cerebella of mutant mice in which the Purkinje cell (pcd) or the granular cell layer (weaver) is missing. These data suggest that the c-Kit protein is produced not by the Purkinje cell nor by the granular cell but by the cells present in the molecular layer and that the protein is then transported to the region around the Purkinje cell soma. This interpretation was supported by in situ hybridization analysis: cells containing the c-kit transcripts were found only in the molecular layer, while the granular and Purkinje cells were negative.

Alleles↗
PubMed1981

Expression of glial antigens C1 and M1 in developing and adult neurologically mutant mice.

The distribution of two glial antigens (C1 and M1) has been studied by indirect immunofluorescence during postnatal development of the cerebella of normal and neurologically mutant mice (weaver, staggerer, reeler, Purkinje cell degeneration, and wobbler). During the first postnatal week of normal development, C1 antigen is expressed in ependyma. Bergmann glial fibers (BG), and astrocytes of the internal granular layer and white matter. After day 10, C1 antigen is restricted to BG and ependymal cells. During the second and third week. BG undergo a transient loss of C1 antigen that starts in medioventral areas and spreads in a gradient dorsally and laterally. In reeler, weaver, and staggerer, C1 antigen expression is normal during the first postnatal week, and subsides in BG in a similar spatial gradient as described for the normal littermates. However, the loss of C1 antigen in BG occurs earlier (first in reeler, then in weaver, and last in staggerer) and is not reversible as it is in normal mice. In Purkinje cell degeneration, C1 antigen expression is diminished in BG after the onset of behavioral abnormalities. Wobbler is normal with respect to C1 antigen expression at adult ages. M1 antigen is detectable in white matter astrocytes from postnatal day 7 on, and persists in these cells into adulthood. Astrocytes if the internal granular layer and BG express M1 antigen only transiently in normal mice during the second and third weeks. The appearance of M1 antigen in BG occurs in a spatiotemporal gradient, matching the one in which C1 antigen disappears. M1 antigen expression is abnormally maintained in BG of reeler, staggerer, and weaver. In Purkinje cell degeneration. M1 antigen is expressed abnormally at the onset of behavioral abnormalities first in astrocytes of the internal granular layer and, with growing age, increasingly also in BG. In wobbler, BG do not express M1 antigen. However, astrocytes of the granular layer are abnormally M1 antigen-positive.

Aging↗
PubMed1982

Comparative levels of endogenous myelin basic protein-serum factors (MBP-SFs) in adult and suckling mice (B6CBAF1 and B6C3HF1, strains) and in neurologically mutant mice of the same genetic background.

Normal adult B6C3HF1 and B6CBAF1 mice contained at least 10 times higher levels (1.17 microM) of endogenous myelin basic protein-serum factors (MBP-SFs) than previously found in adult Lewis rats. In rat MBP-SF levels in the adult (0.03 microM) were much less than in the suckling animals (0.74 microM). In mice, by contrast, the adult (1.17 microM) and suckling (0.75 microM) levels were similar. Suckling mice from 9 different neurologically mutant strains and their clinically normal littermates had MBP-SF levels (0.5 microM) slightly below that of normal suckling mice of the same genetic background (0.75 microM).

Animals↗
PubMed1986

Performance of normal and neurological mutant mice on radial arm maze and active avoidance tasks.

The objectives of the present study are to assess the import of gene-imposed structural alterations on behavioral performance and obtain performance data preliminary to studies of experimental mouse chimera behavior. Reeler, staggerer, and weaver neurological mutant, and control B6C3 and ichthyosis mice were tested on radial arm maze and active avoidance tasks. Weaver mice had incapacitating seizures while performing the radial arm maze task and were, therefore, removed from further testing. Staggerer mice displayed a significant deficit on both tasks compared to control mice. Homozygous reeler mice (rl/rl) also had a significant deficit on the active avoidance task compared to +/rl control mice but not significantly poorer than ichthyosis mice. However, their performance on the radial arm maze task, while initially poor, improved so that they performed the task similar to wild-type controls. Three of the reeler mice reached criterion for solving the radial arm maze task. None of the staggerer mice reached criterion. These data are discussed in terms of the value of using neurologically mutant mice in dissecting structural-functional relationships. It is suggested that the behavior of these mutants might point toward specific components of cerebellar involvement in behavioral acts.

Animals↗
PubMedDate not supplied

Serotonin-immunoreactivity in the cerebellum of two neurological mutant mice and the corresponding wild-type genetic stocks.

Using a serotonin (5-HT)-specific antibody, we examined the 5-HTergic innervation of the cerebellum in the normal mouse (+/+) and in two neurological mutants: weaver (wv/wv), which are characterized by a genetically determined loss of granule cells, and 'Purkinje cell degeneration' (pcd/pcd), which are characterized by a genetically determined loss of Purkinje cells. In normal cerebellum, serotonin-immunoreactive (5-HT-ir) fibers are discrete and ascend to all three layers of the cerebellar cortex. Serotonin-immunoreactive fibers have a much higher density in the atrophic cerebella of both weaver and pcd mutants, where they form multidirectional contours. These anatomical findings provide a profile of 5-HT axon innervation of mouse cerebellum and extend previous neurochemical observations on the metabolic state of cerebellar 5-HT in neurological mutants.

Animals↗
PubMed1990

Saxitoxin-sensitive Na+ channels: presynaptic localization in cerebellum and hippocampus of neurological mutant mice.

The autoradiographic distribution of saxitoxin (STX) binding sites associated with voltage-sensitive Na+ channel was studied in the cerebellum of neurological weaver (wv/wv), Purkinje cell degeneration (pcd/pcd), nervous (nr/nr) and reeler (rl/rl) mutant mice. The Purkinje cell layer contains the highest density of STX binding sites in normal mice. High densities were observed in the molecular layer. Intermediate and very low densities were present in the granular layer and the white matter respectively. There was an important decrease of grain density in the molecular layer and Purkinje cell layer of wv/wv cerebellum, where a large majority of granular cells had disappeared. In pcd/pcd and nr/nr mutants, a small decrease was observed in Purkinje cell layer where the Purkinje cells had almost all degenerated. In rl/rl mutants where all neuronal cells were malpositioned, the compacted molecular layer contained an increased STX binding sites density. Conversely the labelling of Purkinje cells areas was decreased. The hippocampal formation of rl/rl mutants presents an homogeneous repartition of the Na+ channel protein in contrast with the laminated distribution observed in normal mice. Our autoradiographic data suggest that a major proportion of STX-sensitive Na+ channels are localized in parallel fibers of granular cells and in axons of basket cells in a presynaptic position. In Purkinje cells, the dendritic arborization seems to be devoid of STX binding sites conversely to somata.

Animals↗
PubMed1982

Development and expression of cytoplasmic antigens in Purkinje cells recognized by monoclonal antibodies. Studies in neurologically mutant mice.

Five monoclonal antibodies reacting with intracellular constituents of Purkinje cells were investigated by means of indirect immunofluorescence on fresh-frozen sections of the cerebellum and retina from developing and adult normal and mutant mice. Antibodies PC1, PC2 and PC3, which recognize Purkinje cells, but no other cerebellar neuron type, label these cells from day 4 onward. PC4 antigen is expressed in addition to Purkinje cells also in granule cells and neurons of deep cerebellar nuclei and appears in Purkinje cells at day 4. M1 antigen (Lagenaur et al. 1980) is first detectable in Purkinje cell bodies by day 5; it is also detectable in deep cerebellar neurons. In the adult retina, only PC4 antigen is detectably expressed and is localized in the inner segments of photoreceptor cells. The neurological mutants weaver, reeler, jimpy and wobbler show detectable levels of these antigens in Purkinje cells. However, the mutants staggerer and Purkinje cell degeneration are abnormal in expression PC1, PC2, PC3, and M1 antigens. Staggerer never starts to express the antigens during development, whereas Purkinje cell degeneration first expresses the antigens, but then loses antigen expression after day 23. PC4 antigen is detectable in the remaining Purkinje cells in staggerer and Purkinje cell degeneration mice at all ages tested in this study. Deep cerebellar neurons are positive for both antigens, PC4 and M1, in all mutants and at all ages studied. In retinas of staggerer and Purkinje cell degeneration mutants. PC4 antigen is normally detectable in the inner segments of photoreceptor cells, even when these have started to degenerate in the case of Purkinje cell degeneration.

Animals↗
PubMed1977

Immunohistochemical studies of Wolfgram proteins in central nervous system of neurological mutant mice.

Immunohistochemical localization of Wolfgram proteins has been studied by the indirect immunoperoxidase technique with Wolfgram protein W1 antibodies in the nervous system of myelin deficient mutant mice: Jimpy, MSD and Quaking. In all these mutants, the myelinated fibers and the oligodendroglial cells (few in number) in the corpus callosum and the white matter of the cerebellum folium show a positive reaction to protein W1. These observations are in accordance with the immunological studies showing that the two major Wolfgram proteins, W1 and W2, of mutant mice have immunological similarities with that of the controls.

Animals↗