Neostriatal dopamine depletion and locomotor abnormalities due to the Albino Swiss rat agu mutation.
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.
Campbell
J M
JM
Laboratory of Human Anatomy, Glasgow University, UK.
Payne
A P
AP
Gilmore
D P
DP
Byrne
J E
JE
Russell
D
D
McGadey
J
J
Clarke
D J
DJ
Davies
R W
RW
Sutcliffe
R G
RG
D000818:Animals; D002452:Cell Count; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D008124:Locomotion / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000502:physiology; D017072:Neostriatum / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000201:enzymology; D010641:Phenotype; D051381:Rats; D011922:Rats, Mutant Strains; D013378:Substantia Nigra / Q000166:cytology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine