Neostriatal dopamine depletion and locomotor abnormalities due to the Albino Swiss rat agu mutation

Neurosci Lett. 1996 Aug 9;213(3):173-6. doi: 10.1016/0304-3940(96)12852-4.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Count
  • Dopamine / metabolism*
  • Female
  • Locomotion / genetics*
  • Male
  • Mutation / physiology
  • Neostriatum / metabolism*
  • Neurons / cytology
  • Neurons / enzymology
  • Phenotype
  • Rats
  • Rats, Mutant Strains*
  • Substantia Nigra / cytology
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Tyrosine 3-Monooxygenase
  • Dopamine