Influence of Age and Strain on Striatal Dopamine Loss in a Genetic Mouse Model of Lesch‐Nyhan Disease

Influence of Age and Strain on Striatal Dopamine Loss in a Genetic Mouse Model of Lesch‐Nyhan... Abstract : Lesch‐Nyhan disease is a neurogenetic disorder caused by deficiency of the purine salvage enzyme hypoxanthine‐guanine phosphoribosyltransferase (HPRT). Affected individuals exhibit a characteristic pattern of neurological and behavioral features attributable in part to dysfunction of basal ganglia dopamine systems. In the current studies, striatal dopamine loss was investigated in five different HPRT‐deficient strains of mice carrying one of two different HPRT gene mutations. Caudoputamen dopamine concentrations were significantly reduced in all five of the strains, with deficits ranging from 50.7 to 61.1%. Mesolimbic dopamine was significantly reduced in only three of the five strains, with a range of 31.6‐38.6%. The reduction of caudoputamen dopamine was age dependent, emerging between 4 and 12 weeks of age. Tyrosine hydroxylase and aromatic amino acid decarboxylase, two enzymes responsible for the synthesis of dopamine, were reduced by 22.4‐37.3 and 22.2‐43.1%, respectively. These results demonstrate that HPRT deficiency is strongly associated with a loss of basal ganglia dopamine. The magnitude of dopamine loss measurable is dependent on the genetic background of the mouse strain used, the basal ganglia sub‐region examined, and the age of the animals at assessment. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neurochemistry Wiley

Influence of Age and Strain on Striatal Dopamine Loss in a Genetic Mouse Model of Lesch‐Nyhan Disease

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Publisher
Wiley Subscription Services, Inc., A Wiley Company
Copyright
© International Society for Neurochemistry
ISSN
0022-3042
eISSN
1471-4159
D.O.I.
10.1046/j.1471-4159.1999.0720225.x
Publisher site
See Article on Publisher Site

Abstract

Abstract : Lesch‐Nyhan disease is a neurogenetic disorder caused by deficiency of the purine salvage enzyme hypoxanthine‐guanine phosphoribosyltransferase (HPRT). Affected individuals exhibit a characteristic pattern of neurological and behavioral features attributable in part to dysfunction of basal ganglia dopamine systems. In the current studies, striatal dopamine loss was investigated in five different HPRT‐deficient strains of mice carrying one of two different HPRT gene mutations. Caudoputamen dopamine concentrations were significantly reduced in all five of the strains, with deficits ranging from 50.7 to 61.1%. Mesolimbic dopamine was significantly reduced in only three of the five strains, with a range of 31.6‐38.6%. The reduction of caudoputamen dopamine was age dependent, emerging between 4 and 12 weeks of age. Tyrosine hydroxylase and aromatic amino acid decarboxylase, two enzymes responsible for the synthesis of dopamine, were reduced by 22.4‐37.3 and 22.2‐43.1%, respectively. These results demonstrate that HPRT deficiency is strongly associated with a loss of basal ganglia dopamine. The magnitude of dopamine loss measurable is dependent on the genetic background of the mouse strain used, the basal ganglia sub‐region examined, and the age of the animals at assessment.

Journal

Journal of NeurochemistryWiley

Published: Jan 1, 1999

Keywords: ; ; ; ; ;

References

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