Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0040822 (tremor)
 18,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The sub-strain of Albino Swiss rat (AS/AGU) is a spontaneous mutation characterised by an ungainly, staggering gait, hindlimb rigidity, whole body tremor and (when symptoms are fully developed) difficulty in initiating movement; it exhibits a progressive decrease in dopaminergic cells within the substantia nigra. A breeding programme involving Albino Swiss (AS) and AS/AGU parent rats was used to produce the F1 offspring of AS x AS/AGU matings and, subsequently, F1 x AS/AGU back crosses. When adult, the movement of all animals was assessed blind by observers on three occasions, each animal being identifiable by a subcutaneous transponder implanted before weaning. All AS/AGU and half the F1 x AS/AGU back cross animals had abnormal gait, while all AS, F1 and the remaining F1 x AS/AGU backcross animals showed normal gait, implying that the mutation is recessive. Brains of males aged 12-15 months (n = 10 per group) were sectioned transversely on a cryostat (-20 degrees C) to produce a cut face just caudal to the anterior commissure (approximately Bregma -0.5 mm) and 1 mm diameter x 1 mm deep micropunches were taken from three areas of the caudate-putamen. Levels of dopamine were measured in all samples by high performance liquid chromatography with electrochemical detection (HPLC-ECD) followed by protein estimation. Levels of dopamine in the dorsal and middle caudate-putamen varied according to a simple inheritance pattern, being high in males from AS, F1 and F1 x AS/AGU back crosses without locomotor impairment, but lower in AS/AGU and F1 x AS/AGU back crosses with disordered gait. Dopamine levels in the ventral caudate-putamen did not show such a clear variation.
 ...
PMID:Neostriatal dopamine depletion and locomotor abnormalities due to the Albino Swiss rat agu mutation. 887 42

The AS/AGU rat is characterised by an ungainly, staggering gait, hind-limb rigidity, whole body tremor and (in older animals) difficulty in initiating movement. Brains of AS and AS/AGU males aged between 3 and 12 months (n = 10 per group) were sectioned transversely on a cryostat (-20 degrees C) to produce two successive cut faces (corresponding approximately to Bregma +1.2 and -0.5 mm) and 1 mm diameter x 1 mm deep micropunches were taken from four areas of the caudate-putamen. Levels of dopamine in all four areas (measured by HPLC-ECD followed by protein estimation) peaked at around 6 months and then declined in AS and AS/AGU rats. In the dorsal and lateral caudate-putamen, dopamine levels were significantly reduced in AS/AGU rats compared to AS controls from 6 months onwards. This provides further evidence that the AS/AGU mutant has impairment of its striatal dopaminergic systems.
 ...
PMID:Age changes in dopamine levels in the corpus striatum of Albino Swiss (AS) and AS/AGU mutant rats. 954 71

The AS/AGU rat is a mutant derived from the Albino Swiss (AS) strain. It is characterized by an ungainly, staggering gait, hind limb rigidity, whole body tremor and, in older animals, difficulty in initiating movement. As and AS/AGU males aged three, six and nine months (n=6 per group) were used to estimate the levels of dopamine and its metabolites in the extracellular fluid of the caudate-putamen. The results indicate a profound loss of dopamine in the extracellular fluid at all age points examined, together with an increase in the concentration of the metabolite 3,4-dihydroxyphenylacetic acid. It is suggested that these changes reflect a defect of dopaminergic neuron function which may underlie the motor disorder seen in these animals.
 ...
PMID:Extracellular levels of dopamine and its metabolite 3,4-dihydroxy-phenylacetic acid measured by microdialysis in the corpus striatum of conscious AS/AGU mutant rats. 962 32

The AS/AGU rat provides an alternative to experimentally produced laboratory models of basal ganglia disorders. This mutant is characterised by disturbances of movement including clumsy gait, whole body tremor, rigidity and difficulty in initiating movement. From an early age, there is a profound depletion of extracellular dopamine in the dorsal caudate-putamen as measured via in vivo microdialysis; levels are only 10-20% of those found in the parent Albino Swiss (AS) strain. Subsequently a depletion of whole tissue dopamine levels occurs and, later still, loss of dopaminergic cells in the substantia nigra pars compacta. The dysfunction in movement and the nigrostriatal dopaminergic system are clearly linked, since movement can be ameliorated by L-DOPA administration. Furthermore, there are depletions in glucose utilisation in several regions of the basal ganglia circuitry, including the substantia nigra pars compacta, the subthalamic nucleus and the ventrolateral thalamus. The AS/AGU rat represents a unique opportunity to investigate the intrinsic factors controlling the integrity of dopaminergic systems and the recent successful positional cloning of the agu gene will allow the molecular mechanisms underlying this interesting phenotype to be analysed.
 ...
PMID:The AS/AGU rat: a spontaneous model of disruption and degeneration in the nigrostriatal dopaminergic system. 1092 93