Disease relevance of Mice, Neurologic Mutants

• The mouse neurological mutant dystonia musculorum (dt) suffers from a hereditary sensory neuropathy [1].
• The propagation of pseudorabies virus (PrV) in the mouse nervous system was studied after intranasal inoculation of a PrV mutant expressing beta-galactosidase after insertion of the Escherichia coli Lac-Z gene into the gene encoding the nonstructural, nonessential glycoprotein gG [2].
• Wobbler, the neurological mutant mouse, carries an autosomal recessive gene (wr) and has been characterized as a model of lower motoneuron disorders with associated muscle atrophy, denervation and reinnervation [3].
• The weaver mice phenotype, characterized by ataxia, tremor, male infertility, and tonic-clonic seizures, is caused by a point mutation in the inwardly rectifier K(+) channel gene KCNJ6 (GIRK2) [4].
• Recent research has raised the interesting possibility that the neurological mutant mouse, wobbler (wr/wr), possesses an estrogen receptor deficit analogous to the androgen receptor deficiency found in androgen-resistant mice with testicular feminization [5].

Psychiatry related information on Mice, Neurologic Mutants

• Reelin mutations in mouse and man: from reeler mouse to schizophrenia, mood disorders, autism and lissencephaly [6].
• Olfactory discrimination learning deficit in heterozygous reeler mice [7].

High impact information on Mice, Neurologic Mutants

• LCH parallels the reeler mouse mutant (Reln(rl)), in which Reln mutations cause cerebellar hypoplasia, abnormal cerebral cortical neuronal migration and abnormal axonal connectivity [8].
• A potassium channel mutation in weaver mice implicates membrane excitability in granule cell differentiation [9].
• We now report that weaver mice have a missense mutation in a gene encoding a G-protein coupled inward rectifier potassium channel [9].
• Here we report that the phenotype of the spontaneous neurological mutant mouse dreher (dr) results from a failure of the roof plate to develop [10].
• These processes are severely disrupted by mutations in reelin which cause widespread misplacement of neurons and associated ataxia in reeler mice [11].

Chemical compound and disease context of Mice, Neurologic Mutants

• NK-cell cytotoxic activity and their relative distributions were studied in the spleen of female Lurcher mice with spontaneous olivopontocerebellar degeneration (C3H) and female athymic nu/nu mice (BALB/c) influenced by 3-acetylpyridine (the neurotoxin causing selective degeneration of cerebellar and inferior olive neurons in some rodent species) [12].

Biological context of Mice, Neurologic Mutants

• A novel protein complex linking the delta 2 glutamate receptor and autophagy: implications for neurodegeneration in lurcher mice [13].
• Loss of Rb activates both p53-dependent and independent cell death pathways in the developing mouse nervous system [14].
• In the embryonic mouse nervous system, CM1 immunoreactivity was detected in neurons undergoing programmed cell death and was markedly increased in Bcl-xL-deficient embryos and decreased in Bax-deficient embryos [15].
• We have studied the transcript distribution of the retinoic acid receptors (RARs) and the cytoplasmic retinoid binding proteins during embryonic development of the mouse nervous system [16].
• Elimination of tPA delayed the apoptotic death of Purkinje and granule neurons in Lurcher mice, and reduced the phosphorylation of Jun and the activation of caspase 8 [17].

Anatomical context of Mice, Neurologic Mutants

• We report here evidence that the mesolimbic and nigrostriatal systems are differentially affected in the mutant mouse weaver, and in particular that dopamine is severely depleted in the dorsal striatum of weaver but relatively spared in the ventral striatum [18].
• Explant culture for 7 d of cerebella isolated from wild-type and reeler mice at embryonic day 13 (E13) reproduced in a phenotype-dependent manner the two distinct arrangement patterns (linear vs clustered) of Purkinje cells [19].
• The importance of reelin in the establishment of GnRH neurons in the hypothalamus was confirmed by our finding that the brains of developing and adult reeler mice of both sexes contained a markedly reduced number of these neuroendocrine neurons [20].
• Reelin, the extracellular matrix protein missing in reeler mice, plays an important role in neuronal migration in the central nervous system [21].
• Different actions of gabapentin and baclofen in hippocampus from weaver mice [22].

Associations of Mice, Neurologic Mutants with chemical compounds

• Neurodegeneration in Lurcher mice caused by mutation in delta2 glutamate receptor gene [23].
• Genetic inactivation of the K-ATP channel pore-forming subunit Kir6.2 resulted in a selective rescue of SN but not VTA DA neurons in two mechanistically distinct mouse models of dopaminergic degeneration, the neurotoxicological 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model and the mutant weaver mouse [24].
• We have previously identified a cell surface glycoprotein of the mouse nervous system named brain cell surface protein-2 (BSP-2) [25].
• We also analyzed the endogenous NSC population in the reeler mouse using bromodeoxyuridine injections [26].
• Protracted l-methionine (6.6 mmolkg for 15 days, twice a day) treatment in mice elicited in brain an increase of S-adenosyl-homocysteine, the processing product of the methyl donor S-adenosyl-methionine, and a marked decrease of reelin and GAD67 mRNAs in both WT and heterozygous reeler mice [27].

Gene context of Mice, Neurologic Mutants

• Seizure activity has been reported in a Girk2 null mutant mouse lacking GIRK2 channels but showing normal cerebellar development as well as in the weaver mouse, which has mutated GIRK2 channels and shows abnormal development [28].
• The mouse neurological mutant flailer expresses a novel hybrid gene derived by exon shuffling between Gnb5 and Myo5a [29].
• Activity and expression pattern of cyclin-dependent kinase 5 in the embryonic mouse nervous system [30].
• To explore in vivo parallels of these findings, we investigated Bag1 expression in the developing mouse nervous system using immunohistochemical methods [31].
• These findings suggest that leptin, a peripheral signal of energy stores in adult animals, is required for normal neuronal and glial maturation in the mouse nervous system [32].

Analytical, diagnostic and therapeutic context of Mice, Neurologic Mutants

• In situ hybridization analysis of Girk2 expression in the developing central nervous system in normal and weaver mice [33].
• To this end we studied by immunocytochemical, in situ hybridization procedures and receptor autoradiography, several markers of the mesotelencephalic dopamine pathway in heterozygous reeler mice and controls [34].
• The fate of embryonic Purkinje cells grafted over the brainstem surface of the adult Lurcher mouse was analyzed using anti-calbindin (CaBP) immunocytochemistry [35].
• Although several alleles of the mouse reeler mutation were identified as disruptions of Reln, there is no other animal model with a confirmed mutation in Reln [36].
• Molecular cloning of novel leucine-rich repeat proteins and their expression in the developing mouse nervous system [37].

References