Disease relevance of Atrn

• The rat zitter (zi) mutation induces hypomyelination and vacuolation in the central nervous system (CNS), which result in early-onset tremor and progressive flaccid paresis [1].
• DA levels in caudate nucleus were significantly lower in adult age (10-12 weeks) SER, which showed epileptic seizures, and zitter rats than in adult Kyo: Wistar and tremor rats [2].
• These changes may be due to a zitter gene, since zitter rats show the same tendency, and they may be related to tonic seizures in SER [3].

High impact information on Atrn

• Attractin/mahogany/zitter plays a critical role in myelination of the central nervous system [1].
• CNS pathology in the neurological mutant rats zitter, tremor and zitter-tremor double mutant (spontaneously epileptic rat, SER). Exaggeration of clinical and neuropathological phenotypes in SER [4].
• Loss of D3 receptors in the zitter mutant rat is not reversed by L-dopa treatment [5].
• In control Sprague-Dawley (SD) and zitter heterozygote (Zi/-) rats that do not show a loss of D(3) receptors with vehicle treatment, L-dopa produced no change in D(3) receptor number or in DA terminal density as measured by dopamine transporter (DAT) binding and tyrosine hydroxylase immunoautoradiography (TH-IR) [5].
• The myelin vacuolation (mv) rat with a null mutation in the attractin gene [6].

Chemical compound and disease context of Atrn

• Dopamine (DA) and norepinephrine (NE) brain levels and turnover rate were examined in the spontaneously epileptic rat (SER: zi/zi, tm/tm), a double mutant rat obtained by mating tremor heterozygotes (tm/+) with zitter homozygotes associated with epileptic seizures composed of spontaneously occurring tonic convulsion and absence-like seizure [2].

Biological context of Atrn

• In the Fz/Atrn cells, accumulation of ROS was repressed, and cell survival against oxidative stress was enhanced to the same level as in Fw cells [7].
• These observations suggested that lack of Atrn gene expression induced neurodegeneration by a decrease in active ERK through an intracellular signaling via oxidative stress [7].
• Interestingly, phosphorylation of ERK was significantly increased in Fz/Atrn cells by H(2)O(2) stimulus, similarly to Fw cells [7].
• Linkage analysis using intercross progeny between the myelin vacuolation (mv) rat, named after the pathologic characteristics, and normal control rat strains showed that the mv phenotypes were cosegregated with polymorphic markers adjacent to the Atrn (Attractin, formerly zi [zitter]) locus on rat chromosome 3 [6].
• Pivotal role of attractin in cell survival under oxidative stress in the zitter rat brain with genetic spongiform encephalopathy [7].

Anatomical context of Atrn

• Rat myelin vacuolation mutation at the Attractin locus (Atrn(mv)) is a genomic deletion including the whole exon 1 of the Atrn gene [8].
• Bmax was significantly increased in the cerebellum and hippocampus of the zitter rats, while KD was not changed, in comparison with Kyoto/Wistar rats and tremor rats [3].
• DA levels in other areas such as thalamus-hypothalamus, midbrain, and pons medulla were not different among SER, zitter, tremor, and Kyo: Wistar rats at age 10-12 weeks [2].
• Dopamine content in the caudate-putamen, nucleus accumbens and olfactory tubercle of zitter rats decreased significantly with age, and was lower than that found in corresponding age-matched controls [9].
• Ultrastructural alterations of the Schwann cells were chronologically examined in zitter and in control rats [10].

Associations of Atrn with chemical compounds

• To test the oxidant stress hypothesis of dopaminergic degeneration, age-related changes in the mesostriatal dopamine neuron system were compared between zitter mutant rats which have abnormal metabolism of oxygen species in the brain and Sprague-Dawley rat as a control using the neurochemistry and immunohistochemistry [9].
• A characteristic decline of tyrosine hydroxylase-immunoreactive fibers in the caudate-putamen of the zitter rat was also observed [9].
• Central type benzodiazepine (BDZ) receptor binding in spontaneously epileptic rats (SER) and their parent strains, tremor rats and zitter rats, and Kyoto/Wistar rats were investigated [3].
• The morphology of the serotoninergic neuron system and the serotonin level in the zitter rat were compared to those of age-matched Sprague-Dawley (SD) rats [11].
• Thus, the zitter rat may provide a good model for studying the neurotoxic effects of superoxide species on the serotoninergic neuron system [11].

Regulatory relationships of Atrn

• Consistently, zitter rat brains express the normal cellular PrP (PrPC), but do not accumulate the protease-resistant modified isoform (PrPSC) [12].

Other interactions of Atrn

• Expression of the BDNF gene was lower in the zitter rat brain (cerebrum, cerebellum, and brainstem regions) [13].
• There was no difference in GSH-Px activity between the brains from zitter and SD/J rats [14].
• These results indicate that PrP is not involved in the pathogenesis of spongiform encephalopathy in zitter rats [12].
• Zitter mutant rats exhibiting a heterogeneous loss of striatal DA innervation were examined for DA transporter (DAT) binding and DA D3 receptor number by autoradiography and compared with Sprague-Dawley rats [15].
• Prominent abnormalities in catalase and D-AAO but not in SOD activity were demonstrated before or at the same time as the appearance of the morphological vacuolation in the brain of suckling zitter rats [14].

Analytical, diagnostic and therapeutic context of Atrn

• A test for allelism suggested that the mv mutation was a new allele in ATRN: In comparison with a marked decrease of Atrn(zi)/Arn(zi), Northern blot analysis revealed no expression of Atrn mRNA in the brain of the mv rats [6].
• Discovery of the rat null mutation Atrn(mv), different from Atrn(zi), provides a new animal model for studying the functions of the attractin protein [6].
• Furthermore, activation of ERK was confirmed in the brains of WTC and zitter rats by Western blot analysis and immunohistochemistry [7].
• Local cerebral glucose utilization (LCGU) in spontaneously epileptic rats (SER) and in their parent strains, zitter (ZI) and Kyoto-Wistar (KW) rats was studied by autoradiography with [14C]2-deoxyglucose [16].
• Obvious RFLV on the locus was not detected in zitter rats by a Southern blot hybridization [12].

References