Skip to main content
SpringerLink
Log in

Animal Models for Lesch-Nyhan Disease

  • Protocol
Animal Models of Neurological Disease, I

Part of the book series: Neuromethods ((NM,volume 21))

Abstract

In 1964, in the Johns Hopkins clinics, Michael Lesch and William Nyhan saw two brothers with cerebral palsy, movement disorder, and an extremely high plasma uric acid (VA) level. Most striking in these patients was compulsive self-mutilatory behavior (SMB) involving intense biting of the digits and lips. Careful metabolic study showed profound hyperuricemia and hyperuricosuria in this syndrome, now known as Lesch-Nyhan disease (LND). When adjusted for body wt, total daily UA excretion was often 100 times normal (Nyhan et al., 1965). Because of the unusual association of hyperuricemia and a behavioral abnormality, other cases were quickly identified, and an X-linked recessive pattern of inheritance was deduced. In 1967, J. E. Seegmiller and his colleagues reported that erythrocytes from patients with LND possessed less than 0.001% of normal activity for the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adamec R. E. and Stark-Adamec C. (1986) Limbic hyperfunction, limbic epilepsy and interictal behavior: Models and methods of detection, in The Limbic System: Functional Organization and Clinical Disorders (Doane B. W. and Livingston K. E., eds.), Raven Press, New York, pp. 129–146.

    Google Scholar 

  • Allsop J. and Watts R. W. E. (1980) Activities of amidophospho-ribosyltransferase and purine phospho-ribosyltransferases and the phosphoribosylpyro-phosphate content of rat central nervous system at different stages of development. J. Neurol. Sci. 46, 221–238.

    Article  PubMed  CAS  Google Scholar 

  • Altar C. A., Marien M. R., and Marshall J. F. (1987) Time course of adaptations in dopamine biosynthesis, metabolism and release following nigrostriatal lesions: Implications for behavioral recovery from brain injury. J. Neurochem. 43, 390–399.

    Article  Google Scholar 

  • Alvares A. P., Anderson K. E., Conney A. H., and Kappas A. (1976) Interactions between nutritional factors and drug biotransformations in man. Proc. Natl. Acad. Sci. USA 73, 2501–2504.

    Article  PubMed  CAS  Google Scholar 

  • Anders T. F., Cann H. M., Ciaranello R. D., Barchas J. D., and Berger P. A. (1978) Further observations on the use of 5-hydroxytryptophan in a child with Lesch-Nyhan syndrome. Neuropaediatrie 76, 351–355.

    Google Scholar 

  • Barshop B. A., Alberts A. S., Laikind P., and Gruber H. E. (1989) Studies of mutant human adenylosuccinate lyase. Adv. Exp. Biol. Med. 253A, 23–30.

    Article  CAS  Google Scholar 

  • Ben-Ari Y. and Kelly J. S. (1976) Dopamine evoked inhibition of single cells of the feline putamen and basolateral amygdala. J. Physiol. 256, 1–21.

    PubMed  CAS  Google Scholar 

  • Berman P. H., Balis M. E., and Dancis J. (1969) Congenital hyperuricemia, an inborn error of purine metabolism associated with psychomotor retardation, athetosis and self-mutilation. Arch. Neurol. 20, 44–52.

    Article  PubMed  CAS  Google Scholar 

  • Boyd E. M., Dolman M., Knight L. M., and Sheppard E. P. (1965) The chronic oral toxicity of caffeine. Can. J. Physiol. Pharmacol. 43, 995–1007.

    Article  CAS  Google Scholar 

  • Breakefield X. O., Castiglione C. M., and Edelstein S. B. (1976) Monoamine oxidase activity decreased in cells lacking hypoxanthine phosphoribosyltransferase activity. Science 192, 1018–1020.

    Article  PubMed  CAS  Google Scholar 

  • Breese G. R., Baumeister A. A., McCown T. J., Emerick S. G., Frye G. D., Crotty K., and Mueller R. A. (1984) Behavioral differences between neonatal and adult 6-hydroxydopamine-treated rats to dopamine agonists: Relevance to neurological symptoms in clinical syndromes with reduced brain dopamine. J. Pharmacol. Exp. Ther. 231, 343–354.

    PubMed  CAS  Google Scholar 

  • Breese G. R., Baumeister A., Napier T. G, Frye G. D., and Mueller R. A. (1985a) Evidence that D1 dopamine receptors contribute to the super-sensitive behavioral responses induced by L-dihydroxyphenylalanine in rats treated neonatally with 6-hydroxydopamine. J. Pharmacol. Exp. Ther. 234,287–295.

    Google Scholar 

  • Breese G. R., Duncan G. E., Napier T. C., Bondy S. C., Iorio L. C., and Mueller R A. (1987) 6-hydroxydopamine treatments enhance behavioral responses to intracerebral microinjection of D1-and D2-dopamine agonists to nucleus accumbens and striatum without changing dopamine receptor binding. J. Pharmacol. Exp. Ther. 240,167–176.

    PubMed  CAS  Google Scholar 

  • Breese G. R., Napier T. C., and Mueller R. A. (1985b) Dopamine agonist-induced locomotor activity in rats treated with 6-hydroxydoparnine at differing ages: Functional supersensitivity of D1 dopamine receptors in neonatally lesioned rats. J. Phamacol. Exp. Ther. 174, 447–455.

    Google Scholar 

  • Breese G. R. and Traylor T. D. (1960) Effects of 6-hydroxydopamine on brain norepinephrine and dopamine: Evidence for selective degeneration of catacholamine neurons. J. Pharmcol. Exp. Ther. 174, 413–420.

    Google Scholar 

  • Brennand J., Chinault A. G, Konecki D. S., Melton D. W., and Caskey C. T. (1982) Cloned cDNA sequences of the hypoxanthine guanine phosphoribosyltransferase gene from a mouse neuroblastoma cell line found to have amplified genomic sequences. Proc. Natl. Acad. Sci. USA 79, 1950–1954.

    Article  PubMed  CAS  Google Scholar 

  • Brenton D. P., Astrin K. H., Cruikshank M. E., and Seegmiller J. E. (1977) Measurement of free nucleotides in cultured human lymphoid cells using HPLC. Biochem. Med. 17, 231–247.

    Article  PubMed  CAS  Google Scholar 

  • Casas M., Ferre S., Cadafalch J., Grau J. M., and Jane F. (1989) Rotational behaviour induced by theophylline in 6-OHDA nigrostriatal denervated rats is dependent on the supersensitivity of striatal dopaminergic receptors. Pharmcol. Biochem. Behav. 9, 609–613.

    Article  Google Scholar 

  • Casas-Bruge M., Almenar C., Grau J. M., Jane F., Herrera-Marschwitz M., and Ungerstedt U. (1985) Dopaminergic receptor supersensitivity in self-mutilatory behaviour of Lesch-Nyhan disease. Lancet 1, 991–992.

    Article  PubMed  CAS  Google Scholar 

  • Castells S., Chakrabati C., Winsberg B. G., Hurwic M., Perel J. M., and Nyhan W. L. (1979) Effects of L-5-hydroxytryptophan on monoamine and amino acid turnover in the Lesch-Nyhan syndrome. J. Autism Dev. Disord. 9, 95–103.

    Article  PubMed  CAS  Google Scholar 

  • Chamove A. S. and Anderson J. R. (1981) Self-aggression, stereotypy and self-injurious behaviour in man and monkeys. Curr. Psychol. Rev. 1, 245–256.

    Article  Google Scholar 

  • Chang S. M., Wager-Smith R., Tsao T. Y., Henkel-Tigges J., Vaishn M., and Caskey C. T. (1987) Construction of a defective retrovirus encoding the human hypoxanthine phosphoribosyltransferase cDNA and its expression in cultured cells in mouse bone marrow. Mol. Cell. Biol. 7, 854–861.

    PubMed  CAS  Google Scholar 

  • Cools A. R. and van Rossum J. M. (1980) Multiple receptors for brain dopamine in behaviour regulation. Life Sci. 27, 1237–1253.

    Article  PubMed  CAS  Google Scholar 

  • Corradetti R., Lo Conte G., Moroni F., Passani M. B., and Pepeu G. (1984) Adenosine decreases aspartate and glutamate release from rat hippocampal slices. Eur. J. Pharmcol. 104, 19–26.

    Article  CAS  Google Scholar 

  • Creese I., Burt D. R., and Snyder S. H. (1977) Dopamine receptor binding enhancement accompanies lesion-induced behavioral supersensitivity. Science 197, 596–598.

    Article  PubMed  CAS  Google Scholar 

  • Criswell, H, Mueller R. A., and Breese G. R. (1987) Assessment of purine-dopamine interactions in 6-hydroxydopamine-lesioned rats: Evidence for pre-and postsynaptic influences by adenosine. J. Pharmacol. Exp. Ther. 244, 493–500.

    Google Scholar 

  • Crussi F. G., Robertson D. M., and Hiscox I. L. (1969) The pathological condition of the Lesch-Nyhan syndrome. Am. J Dis. Child. 116, 501–506.

    Google Scholar 

  • Daly J. W., Bruns R. F., and Snyder S. H. (1981) Adenosine receptors in the central nervous system: Relationship to the central actions of methylxanthines. Life Sci. 28, 2083–2097.

    Article  PubMed  CAS  Google Scholar 

  • De Mars R. (1971) Genetic studies of HG-PRT Deficiency and the Lesch-Nyhan syndrome with cultured human cells. Fed. Proc. 30, 944–955.

    Google Scholar 

  • Demopoulos H. B., Flamm E. S., Pietronigro D. D., and Seligman M. L. (1980) The free radical pathology and the microclrculation ln the major central nervous system disorders. Acta Physiol. Scand. (Suppl.), 492 91–119.

    CAS  Google Scholar 

  • Dennis S. G. and Melzack R. (1979) Self-mutilation after dorsal rhizotomy in rats: Effects of prior pain and pattern of root lesions. Exp. Neurol. 65, 412–421.

    Article  PubMed  CAS  Google Scholar 

  • Dewey M. J., Martin D. W., Jr., Martin G. R., and Mintz B. (1977) Mosaic mice with teratocarcinoma-derived mutant cells deficient in hypoxantbinephosphoribosyltransferase. Proc. Natl. Acad Sci. USA 74, 5564–5568.

    Article  PubMed  CAS  Google Scholar 

  • Duncan G. E., Criswell H. E., McCown T. J., Paul I. A., Mueller R. A., and Breese G. R. (1987) Behavioral and neurochemical responses to haloperidol and SCH-23390 in rats treated neonatally or as adults with 6-hydroxydopamine. J. Pharmacol. Exp. Ther. 243, 1027–1034.

    PubMed  CAS  Google Scholar 

  • Dunnett S. B., Sirinathsinghji D. J. S., Heavens R., Rogers D. C., and Kuehn M. R. (1989) Monoamine deficiency in a transgenic HPRT mouse model of Lesch-Nyhan syndrome. Brain Res. 501, 401–406.

    Article  PubMed  CAS  Google Scholar 

  • Dunwiddie T. V. (1985) The physiological role of adenosine in the central nervous system. Int. Rev. Neurobiol. 27, 63–82.

    Article  PubMed  CAS  Google Scholar 

  • Edwards N. L., Johnston M. V., and Silverstein F. S. (1989) Cerebrospinal fluid cyclic nucleotide alterations in the Lesch-Nyhan syndrome. Adv. Exp. Biol. Med. 253A, 181–188.

    Article  CAS  Google Scholar 

  • Ellison G., Eison M. S., Huberman H. S., and Daniel F. (1978) Long-term changes in dopaminergic innervation of caudate nucleus after continuous amphetamine administration. Science 201, 276–278.

    Article  PubMed  CAS  Google Scholar 

  • Evans M. C., Swan J. H., and Meldrum B. S. (1987) An adenosine analogue protects against long term development of ischemic cell loss ln the rat hippocampus. Neurosci. Lett. 83, 287–292.

    Article  PubMed  CAS  Google Scholar 

  • Ferre S., Casas M., Cobos A., Garcia C., Jane F., and Grau J. M. (1987) L-dopa causes an acute, partial and reversible reversal of denervation-induced supersensitivity of striatal dopaminergic receptors. Psychopharmacology 91,254–256.

    Article  PubMed  CAS  Google Scholar 

  • Ferrer I., Costell M., and Grisolia S. (1982) Lesch-Nyhan syndrome-like behavior in rats from caffeine ingestion. FEBS Lett. 141, 275–278.

    Article  PubMed  CAS  Google Scholar 

  • Finger S., Heavens R. P., Sirinathsinghji D. J. S., Kuehn M. R., and Dunnett S. B. (1988) Behavioral and neurochemical evaluation of a transgenic mouse model of Lesch-Nyhan syndrome. J. Neurol. Sci. 86,459–461.

    Article  Google Scholar 

  • Fox I. H. and Kelley W. N. (1971) Phosphoribosylpyrophosphate in man: Biochemical and clinical significance. Ann. Intern. Med. 74, 424–436.

    Article  PubMed  CAS  Google Scholar 

  • Fredholm B. B., Herrera-Marschitz M., Jonzon B., Lindstrom K., and Ungerstedt U. (1983) On the mechanism by which methylxanthines enhance apomorphine-induced rotation behavior in the rat. Pharmacol. Biochem. Behav. 19, 535–541.

    Article  PubMed  CAS  Google Scholar 

  • Fridovich I. (1983) Superoxide radical: An endogenous toxicant. Ann. Rev. Toxicol. 23, 239–257.

    Article  CAS  Google Scholar 

  • Frith C. D., Johnstone E. C., Joseph M. H., Powell R.J., and Watts R. W. E. (1976) Double-blind clinical trial of 5-hydroxytryptophan in a case of Lesch-Nyhan syndrome. J. Neurol. Neurosurg. Psychiatr. 39, 656–662.

    Article  PubMed  CAS  Google Scholar 

  • Fuxe K. and Ungerstedt U. (1974) Action of caffeine and theophylline on supersensitive dopamine receptors. Med. Biol. 52,48–54.

    PubMed  CAS  Google Scholar 

  • Garrod A. E. (1908) Inborn errors of metabolism (Croonian Lectures). Lancet 1,73, 142–214.

    Google Scholar 

  • Goldstein M., Anderson L. T., Reuben R., and Dancis J. (1985) Self-mutilation in Lesch-Nyhan disease is caused by dopaminergic denervation. Lancet 1, 338,339.

    Google Scholar 

  • Goldstein M., Battista A. H., Ohmoto T., Anagoste B., and Fuxe K. (1973) Tremor and involuntary movements in monkeys: Effect of L-dopa and of a dopamine receptor stimulating agent. Science 179, 816,817.

    Article  PubMed  CAS  Google Scholar 

  • Goldstein M, Kuga S., Kusano N., Meller E., Dancis J., and Schwartz R. (1986) Dopamine agonist induced self-mutilative biting behavior in monkeys with unilateral ventromedial tegmental lesions of the brainstem: Possible pharmacological model for Lesch-Nyhan syndrome. Brain Res. 367, 114–129.

    Article  PubMed  CAS  Google Scholar 

  • Gordon R. B., Stout J. T., Emmerson B. Y., and Caskey C. T. (1987) Molecular studies of hypoxanthine-guanine phosphoribosyltransferase mutations in 6 New Zealand families. Ann. N. Z. J. Med. 17, 424–433.

    Article  CAS  Google Scholar 

  • Green R. D., Proudfit H. K., and Yeung S. H. (1982) Modulation of striatal doparninergic function by local inection of 5′-N-ethylcarboxamide adenosine. Science 218,58–61.

    Article  PubMed  CAS  Google Scholar 

  • Greene M. L., Boyle J. A., and Seegmiller J. E. (1970) Substrate stabilization: Genetically controlled reciprocal relationship of two human enzymes. Science 167,337–340.

    Article  Google Scholar 

  • Hagberg H., Andersson P., Butcher S., Sandberg M., Lehmann A., and Hamberger A. (1986) Blockade of NMDA sensitive receptors inhibits ischaemia-induced accumulation of purine catabolites in the rat striatum. Neurosci. Lett. 68, 311–316.

    Article  PubMed  CAS  Google Scholar 

  • Harkness R. A. (1989) Lesch-Nyhan syndrome: Reduced amino acid concentrations in CSF and brain. Adv. Exp. Biol. Med. 253A, 159–163.

    Article  CAS  Google Scholar 

  • Harkness R. A., McCreanor G. M., and Watts R. W. E. (1988) Lesch-Nyhan syndrome and its pathogenesis: Purine concentrations in plasma and urine with metabolite profiles in CSF. J. Inherited Metab. Dis. 11, 239–252.

    Article  PubMed  CAS  Google Scholar 

  • Hartgraves S. L and Randall P. K. (1986) Dopamine agonist-induced stereotypic grooming and self-mutilation following striatal dopamine depletion. Psychopharmacology 90,358–363.

    Article  PubMed  CAS  Google Scholar 

  • Hefti F., Melamed E., and Wurtman R. J. (1980) Partial lesions of the dopaminergic nigrostriatal system in rat brain. Brain Res. 195, 123–137.

    Article  PubMed  CAS  Google Scholar 

  • Heikkila R., and Cohen G. (1972) Further studies on the generation of hydrogen peroxide by 6OHDA. Mol. Pharmacology 8, 241–248.

    CAS  Google Scholar 

  • Heikkila R, Shapiro B. S., and Duvoisin R. C.3(1981) The relationship between loss of dopamine nerve terminals, striatal [3H] spiroperidol binding and rotational behavior in unilaterally 6-hydroxydopamine-lesioned rats. Brain Res. 211, 285–292.

    Article  PubMed  CAS  Google Scholar 

  • Hershfield M. S. and Seegmiller J. E. (1977) Regulation of de novo purine synthesis in human lymphoblasts. J. Biol. Chem. 252, 6002–6009.

    PubMed  CAS  Google Scholar 

  • Heshka T. W. (1989) Effects of hypoxanthine on dopamine neurons. Unpublished Masters thesis, McGill University, Montreal, Canada.

    Google Scholar 

  • Hirschhorn R., Papageorgiou P. S., Kesarwala H. H., and Taft L. T. (1980) Amelioration of neurologic abnormalities after “ezyme replacement” in adenosine deaminase deficiency. N. Engl. J. Med. 303, 377–830.

    Article  PubMed  CAS  Google Scholar 

  • Hoefnagel D., Andrew E. D., Mireault N. G., and Berndt W. O. (1965) Hereditary choreoathetosis, self-mutilation and hyperuricemia in young males. N. Eng.J. Med. 273, 130–134.

    Article  CAS  Google Scholar 

  • Hooper M., Hardy K., Handyside A., Hunter S., and Monk M. (1987) HPRT deficient (Lesch-Nyhan) mouse embryos derived from germline colonization by cultured cells. Nature 326, 292–295.

    Article  PubMed  CAS  Google Scholar 

  • Hornykiewicz O. (1981) Brain neurotransmitter changes in Parkinson’s disease, in Neurology 2: Movement Disorders (Marsden C. D. and Fahn S., eds.), Butterworths, London, pp. 41–58.

    Google Scholar 

  • Jankovic J., Caskey C. T., Stout J. T., and Butler I. J. (1988) Lesch-Nyhan syndrome: A study of motor behavior and cerebrospinal fluid neuro-transmitters. Ann. Neurol. 23, 466–475.

    Article  PubMed  CAS  Google Scholar 

  • Jolly D. J., Esty A. C., Bernard H. V., and Friedmann T. (1982) Isolation of a genomic clone partially encoding human hypoxanthine phosphoribosyltransferase. Proc. Natl. Acad. Sci. USA 79, 5038–5042.

    Article  PubMed  CAS  Google Scholar 

  • Jolly D. J., Okayama H., Berg P., Esty A. C., Pilpula D., Bohlen P., Johnson G. G., Scively J. E., Hunkapillar T. J. and Friedmann T. (1983) Isolation and characterization of a full-length expression cDNA for human hypoxanthine phosphoribosyltransferase. Proc. Nalt. Acad. Sci. USA 80, 477–481.

    Article  CAS  Google Scholar 

  • Jones I. H. and Barraclough B. M. (1978) Auto-mutilation in animals and its relevance to self-injury in man. Acta. Psychiatr. Scand. 58, 40–47.

    Article  PubMed  CAS  Google Scholar 

  • Joyce E. M. and Koob G. F. (1981) Amphetamine-, scopolamine-and caffeine-induced locomotor activity following 6-hydroxydopamine lesions of the mesolimbic dopamine system. Psychopharmacology 73, 311–313.

    Article  PubMed  CAS  Google Scholar 

  • Kanazawa I., Kimura M., Murata M., Tanaka Y., and Cho F. (1990) Choreic movements in the macaque monkey induced by kainic acid lesions of the striatum combined with L-dopa. Brain 113, 509–535.

    Article  PubMed  Google Scholar 

  • Katsuragi T., Ushijima I., and Furukawa T. (1983) The clonidine-induced self-injurious behavior of mice involves purinergic mechanisms. Pharmacol. Biochem. Behav. 20, 943–946.

    Article  Google Scholar 

  • Kelley W. N., Greene M. L., Rosenbloom F. M., Henderson J. F., and Seegmiller J. E. (1969) Hypoxanthine-guanine phosphoribosyltransferase deficiency in gout. Ann. Intern. Med. 70, 155–206.

    Article  PubMed  CAS  Google Scholar 

  • Kelley W. N., Rosenbloom F. M., Henderson J, R., and Seegmiller J. E. (1967) A specific enzyme defect in gout associated with overproducton of uric acid. Proc. Natl. Acad. Sci. USA 64, 1735–1738.

    Article  Google Scholar 

  • Kelley W. N. and Wyngaarden J. B. (1983) Clinical syndromes associated with hypoxanthine-guanine phosphoribosyltransferase deficiency, in The Metabolic Basis of Inherited Disease, 5th Ed. (Stanbury J. B., Wyngaarden J. B., Frederickson D. S., Goldstein J. L., and Brown M. S., eds.), McGraw-Hill, New York, pp. 1115–1143.

    Google Scholar 

  • Kiebling M., Lindl T., and Cramer H. (1975) Cyclic adenosinemonophosphate in cerebrospinal fluid. Arch. Psychiatr. Nervenkr. 220, 325–333.

    Article  Google Scholar 

  • Kish S. J., Fox I. H., Kapur B. M., Lloyd K., and Hornykiewicz O. (1985) Brain benzodiazepine receptor binding and purine concentration in Lesch-Nyhan syndrome. Brain Res. 336, 117–123.

    Article  PubMed  CAS  Google Scholar 

  • Kopin I. (1987) Neurotoxins affecting biogenic aminergic neurons. Psychopharmacoloy: The Third Generation of Progress, Raven Press, New York, pp. 351–358.

    Google Scholar 

  • Kuehn M. R., Bradley A., Robertson E. J., and Evans M. J. (1987) A potential animal model for Lesch-Nyhan syndrome through introduction of HPRT mutations into mice. Nature 326, 295–297.

    Article  PubMed  CAS  Google Scholar 

  • Lake C. R. and Ziegler M. G. (1977) Lesch-Nyhan syndrome: Low dopamine-β-hydroxylase activity and diminished sympathetic response to stress and posture. Science 196, 905,906.

    Article  PubMed  CAS  Google Scholar 

  • Lal S. and Sourkes T. L. (1973) Ontogeny of stereotyped behavior induced by apomorphine and amphetamine in the rat. Arch. Int. Pharmacodyn. Ther. 202, 171–182.

    PubMed  CAS  Google Scholar 

  • Lal S. and Sourkes T. L. (1974) Apomorphine derivatives and dopaminergic activity. Adv. Neurol. 5, 307, 308.

    PubMed  CAS  Google Scholar 

  • Lau K. F. and Henderson J. F. (1971) Inhibitors of hypoxanthine-guanine phosphoribosyltransferase. Cancer Chemother. Rep. (Part 2), 3, 87–94.

    Google Scholar 

  • Lesch M. and Nyhan W. L. (1964) A familial disorder of uric acid metabolism and central nervous function. Am. J Med. 36,561–570.

    Article  PubMed  CAS  Google Scholar 

  • Levitt M. (1985) Dysesthesias and self-mutilation in humans and subhumans: A review of clinical and experimental studies. Brain Res. Rev. 10, 247–290.

    Article  Google Scholar 

  • Lloyd H. G. E. and Stone T. W. (1981) Chronic methylxanthine treatment in rats: A comparison of Wistar and Fischer 344 strains. Pharmol. Biochem. Behav. 14, 827–830.

    Article  CAS  Google Scholar 

  • Lloyd K. G., Hornykiewicz O., Davidson L., Shannak K., Farley I., Goldstein M., Shibuya M., Kelley W. N., and Fox I. H. (1981) Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome. N. Engl. J. Med. 305, 1106–1111.

    Article  PubMed  CAS  Google Scholar 

  • Lloyd K. G., Willigens M. T., and Goldstein M. (1985) Induction and reversal of dopamine dyskinesia in rat, cat and monkey. Psychopharmacology 89(Suppl. 21), 200–210.

    Google Scholar 

  • Mark V. H. and Ervin F. R. (1970) Violence and the Brain Harper and Row, New York.

    Google Scholar 

  • McCord J. M. (1985) Oxygen-derived free radicals in post-ischemic tissue injury. N. Engl. J. Med. 312, 159–163

    Article  PubMed  CAS  Google Scholar 

  • McKeran R. O. and Watts R. W. E (1976) Use of phytohaemagglutinin stimulated lymphocytes to study effects of HGPRT deficiency on polynucleotide and protein synthesis in the Lesch-Nyhan syndrome. J. Med. Genet. 13, 91–95.

    Article  PubMed  CAS  Google Scholar 

  • McLean P. D. (1958) The limbic system with respect to self-preservation and the preservation of the species. J. Nerv. Ment. Dis. 127, 1–11.

    Article  Google Scholar 

  • Mehta S., Mitchell D., Roitman D., Kattan A. K., Palmour R. M., and Goodyer P. (1990) Nephrogenic diabetes insipidus as the early renal manefstation of Lesch-Nyhan disease. J. Pediatr.

    Google Scholar 

  • Minana M. D., Portoles M., Jorda A., and Grisolia S. (1984) Lesch-Nyhan syndrome, caffeine model: Increase of purine and pyrimidine enzymes in rat brain. J. Neurochem. 43, 1556–1560.

    Article  PubMed  CAS  Google Scholar 

  • Mizuno T. (1986) Long-term followup of two patients with Lesch-Nyhan syndrome. Neuropediatrics 17, 158–169.

    Article  PubMed  CAS  Google Scholar 

  • Mizuno T.-I. and Yugari Y. (1974) Self-mutilation in Lesch-Nyhan syndrome. Lancet 1, 761.

    Article  PubMed  CAS  Google Scholar 

  • Moore K. E. and Kelly P. H. (1976) Biochemical pharmacology of mesolimbic and mesocortical dopaminergic neurons, in Psychopharmacology: A Generation of Progress (Lipton M. A., DiMascio A., and Killa K. F., eds.), Raven Press, New York, pp. 221–234.

    Google Scholar 

  • Morgan L. L., Schneiderman N., and Nyhan W. L. (1970) Theophylline: Induction of self-biting in rabbits. Psycbon. Sci. 19, 37,38.

    Google Scholar 

  • Mueller K. and Hsiao S. (1980) Pemoline-induced self-biting in rats and self-mutilation in the deLange syndrome. Pharmacol. Biochem. Behav. 13, 627–631.

    Article  PubMed  CAS  Google Scholar 

  • Mueller K. and Nyhan W. L. (1982) Pharmacological control of self-injurious behavior in rats. Pharmacol. Biochem. Behav. 16, 957–963.

    Article  PubMed  CAS  Google Scholar 

  • Mueller K. and Nyhan W. L. (1983) Clonidine potentiates drug induced self-injurious behavior in rats. Pharmacol. Biochem. Behav. 18, 891–894.

    Article  PubMed  CAS  Google Scholar 

  • Mueller K., Saboda S., Palmour R., and Nyhan W. L. (1982) Self-injurious behavior produced in rats by daily caffeine and continuous amphetamine. Pharmacol. Biochem. Behav 17, 613–617.

    Article  PubMed  CAS  Google Scholar 

  • Myers S. and Pugsley T. A. (1986) Decrease in rat striatal dopamine synthesis and metabolism in vivo by metabolically stable adenosine receptor agonists. Brain Res. 375, 193–197.

    Article  PubMed  CAS  Google Scholar 

  • Nauta W. J. H. (1986) Circuitous connections linking cerebral cortex, limbic system and corpus striatum, in The Limbic System: Functional Organization and Clinical Disorders (Doane B. W. and Livingston K. F., eds.), Raven Press, New York, pp. 43–54

    Google Scholar 

  • Nyhan W. L. (1976) Behavior in the Lesch-Nyhan syndrome. J. Autism Child. Schizophr. 6, 235–252.

    Article  PubMed  CAS  Google Scholar 

  • Nyhan W. L., Johnson H. G., Kaufman I. A., and Jones R. L. (1980) Serotonergic approaches to the modification of behavior in the Lesch-Nyhan syndrome. Appl. Res. Ment. Retard. 1, 25–34.

    Article  PubMed  CAS  Google Scholar 

  • Nyhan W. L., Oliver W.J., and Lesch M. A. (1965) A familial disorder of uric acid metabolism and central nervous system function. J. Pediatr. 67, 257–266.

    Article  Google Scholar 

  • Nyhan W. L., Parkman R., Page T., Gruber H. E., Pyatt J., Jolly D.and Friedmann T. (1986) Bone marrow transplantation in Lesch-Nyhan disease. Adv. Med. Biol. 195A, 167–172.

    Article  Google Scholar 

  • Onali P., Olianas M. C and Bunse B. (1988) Evidence that adenosine A2 and dopamine autoreceptors antagonistically regulate tyrosine hydroxylase activity in rat striatal synaptosomes. Brain Res. 456, 302–309.

    Article  PubMed  CAS  Google Scholar 

  • Page T. and Nyhan W. L. (1989) The spectrum of HPRT deficiency: An update. Adv. Exp. Biol. Med. 253A, 129–133.

    Article  CAS  Google Scholar 

  • Page T., Bakay B., Nissinen E., and Nyhan W. L. (1981) Hypoxanthine-guanine phosphoribosyltransferase variants: correlation of clinical phenotype with enzyme activity. J. Inher. Metab. Dis. 4, 203–218.

    Article  PubMed  CAS  Google Scholar 

  • Palmour R. M., Dyer C., and Seegmiller J. E. (1985) Kinetic alterations of adenosine receptors in HPRT deficient neuroblastoma cells. Adv. Exp. Biol. Med. 195A, 231–234

    Google Scholar 

  • Palmour R. M., Dyer C., Pearce C., Goldman N. J., and Seegmiller J. E. (1990a) Caffeine-induced self-mutilation in rats: A critical appraisal. Brain Res.

    Google Scholar 

  • Palmour R. M., Schucher K., Pacheco P., and Ervin F. R. (1990b) Dopamine depletion and self-mutilation in the rat: A model for Lesch-Nyhan disease. Phamacol. Biochem. Behav.

    Google Scholar 

  • Palmour R. M., Goodyer P., Reade T., and Chang T. M. S. (1989) Microencapsulated xanthine oxidase as an experimental therapy in Lesch-Nyhan disease. Lancet 2, 687, 688.

    Article  PubMed  CAS  Google Scholar 

  • Palmour R. M., Heshka T. W., and Ervin F. R. (1989) Hypoxanthine accumulation and dopamine depletion in Lesch-Nyhan disease: An anima1 model. Adv. Exptl. Biol. Med. 253A, 165–172.

    Article  CAS  Google Scholar 

  • Palmour R. M. and Pearce C. J. (1979) Behavioral and neurochemical studies of Lesch-Nyhan’s syndrome. Dev. Psychiatr. 2, 155–160.

    Google Scholar 

  • Papez J. W. (1937) A proposed mechanism of emotion. Arch. Neurol. Psychiar. 38, 725–743.

    Article  Google Scholar 

  • Partington M. W. and Hennen B. K. E. (1967) The Lesch-Nyhan syndrome: Self-destructive biting, mental retardation, neurological disorder and hyperuricemia. Develop. Med. Child. Neurol. 9, 563–572.

    Article  PubMed  CAS  Google Scholar 

  • Penney J. B. Jr. and Young A. B. (1983) Speculations on the functional anatomy of basal ganglia disorders. Ann. Rev. Neurosci. 6, 73–94.

    Article  PubMed  Google Scholar 

  • Peters J. M. (1967) Caffeine-induced hemorrhagic automutilation. Arch. Int. Pharmacodyn. 169, 139–146.

    PubMed  CAS  Google Scholar 

  • Pinsky L. and DiGeorge A. M. (1966) Congenital familial sensory neuropathy with anhidrosis. J. Pediatr. 68, 1–8.

    Article  PubMed  CAS  Google Scholar 

  • Porter N. M., Radulovacki M., and Green R. D. (1988) Desensitization of adenosine and dopamine receptors in rat brain after treatment with adenosine analogs. J. Pharmcol. Exp. Therap. 244, 220–225.

    Google Scholar 

  • Randrup A. and Munkvad I. (1967) Stereotyped activities produced by amphetamine in several animal species and man. Psychopharmacalogia 11, 300–310.

    Article  CAS  Google Scholar 

  • Rassin D. K., Lloyd K. G., Kelley W. N., and Fox I. (1982) Decreased amino acids in various brain areas of patients with Lesch-Nyhan syndrome. Neuropediatrics 13, 130–134.

    Article  PubMed  CAS  Google Scholar 

  • Razzak A., Fujiwara M., and Ueki S. (1975) Automutilation induced by clonidine in mice. Eur.J. Pharmacol. 30, 356–359.

    Article  PubMed  CAS  Google Scholar 

  • Rockson S., Stone R., van der Weyden M., and Kelley W. N. (1974) Lesch-Nyhan syndrome: Evidence for abnormal adrenergic function. Science 166, 934–935.

    Article  Google Scholar 

  • Rosenbloom F. J., Henderson J. F., Caldwell I. C., Kelley W. N., and Seegmiller J. E. (1968) Biochemical basis of accelerated purine biosynthesis de novo in fibroblasts lacking HPRT. J. Biol. Chem. 243, 1166–1173.

    PubMed  CAS  Google Scholar 

  • Rosenbloom F. M., Kelley W. N., Miller J., Henderson J. F., and Seegmiller J. E. (1967) Inherited disorder of purine metabolism: correlation between central nervous system dysfunction and biochemical defects. J. Amer. Med. Assoc. 202, 175–177.

    Article  CAS  Google Scholar 

  • Roth R. H., Wolf M. E., and Deutch A. Y. (1987) Neurochemistry of mid-brain dopamine systems, in Pschopharmcology: The Third Generation of Progress (Meltzer H. Y., ed.), Raven Press, New York, pp. 81–94.

    Google Scholar 

  • Rothman S. M. and Olney J. W. (1986) Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann. Neurol. 19,105–111.

    Article  PubMed  CAS  Google Scholar 

  • Sakata T. and Fuchimoto H. (1973) Stereotyped and aggressive behavior induced by sustained high dose of theophylline in rats. Japan. J. Pharmacol. 23,781–785.

    Article  CAS  Google Scholar 

  • Sass J. K., Itabashi H. H., and Dexter R.A. (1965) Juvenile gout with brain involvement. Arch. Neurol. 13, 639–655.

    Article  PubMed  CAS  Google Scholar 

  • Schloberg A. J., Fernstrom J. D., Kopzynski C., Cusack B. M., and Gillis M. A. (1981) Acute effects of caffeine injection on neutral amino acids and brain monoamine levels in rats. Life Sci. 29, 173–183.

    Article  Google Scholar 

  • Seegmiller J. E. (1976) Inherited deficiency of hypoxanthine guanine phosphoribosyltransferase in X-linked uric aciduria (the lesch-nyhan syndrome and its variants). Acta Human Genet. 6, 75–163.

    CAS  Google Scholar 

  • Seegmiller J. E. (1980) Diseases of purine and pyrimidine metabolism, in Metabolic Control and Disease (Bondy P. K. and Rosenberg L. E., eds.), W. G. Saunders, Philadelphia, pp. 777–937.

    Google Scholar 

  • Seegmiller J. E., Rosenbloom F. M., and Kelley W. N. (1967) Enzyme defect associated with a sex-linked human neurological disorder and excessive purine synthesis. Science 155,1682–1684.

    Article  PubMed  CAS  Google Scholar 

  • Segal D. S., Weinberger S. B., Cahill J., and McCunney S. J. (1980) Multiple daily amphetamine administration: Behavioral and neurochemical alterations. Science 207, 904–907.

    Article  PubMed  CAS  Google Scholar 

  • Silverstein F. S., Johnson M. V., Hutchinson R. J. and Edwards N. L. (1985) Lesch-Nyhan syndrome: CSF neurotransmitter abnormalities. Neurology 35, 907–911.

    Article  PubMed  CAS  Google Scholar 

  • Simmonds H. A., Fairbanks L. D., Morris G. S., Morgan G., Watson A. R., Timms P., and Sigh B. (1987) Central nervous system dysfunction and erythrocyte guanosine triphosphate depletion in purine nucleo-side phosphorylase deficiency. Arch. Dis. Childhood 62,385–391.

    Article  CAS  Google Scholar 

  • Skaper S. and Seegmiller J. E. (1976) Hypoxanthine-guanine phosphoribosyltransferase mutant glioma cells: Diminished monoamine oxidase activity. Science 194, 1171–1173.

    Article  PubMed  CAS  Google Scholar 

  • Slivka A. and Cohen G. (1985) Hydroxyl radical attack on dopamine. J. Biol. Chem. 260, 15,466–15,472.

    PubMed  CAS  Google Scholar 

  • Smellie F. W., Davis C.W., Daly J. W., and Wells J. N. (1979) Alkylxanthines: Inhibition of adenosine-elicited accumulation of cyclic AMP in brain slices and of phosphodiesterase activity. Life Sci. 24, 2475–2482.

    Article  PubMed  CAS  Google Scholar 

  • Snyder F. F., Cruikshank M. K., and Seegmiller J. E. (1978) Comparison of purine metabolism and nucleotide pools in normal and HPRT-neuro-blastoma Biochim. Biophys. Acta 543,556–569.

    Article  PubMed  CAS  Google Scholar 

  • Snyder S. H. (1985) Adenosine as a neuromodulator. Ann. Rev. Neurosci. 8, 103–124.

    Article  PubMed  CAS  Google Scholar 

  • Sprugel W., Mitznegg P., and Heim F. (1977) The influence of caffeine and theobromine on locomotive activity and the brain cGMP/cAMP ratio in white mice. Biochem. Pharmacol. 26, 1723,1724.

    Article  PubMed  CAS  Google Scholar 

  • Stefanovich V. (1979) Influence of theophylline on concentrations of cyclic 3′,5′-adenosine monophosphate and cyclic 3′5′-guanosine monophosphate of rat brain. Neurochem. Res. 4,587–594.

    Article  PubMed  CAS  Google Scholar 

  • Stone T. W. (1981) Physiological roles for adenosine and adenosine 5′-triphosphate in the nervous system. Neuroscience 6, 523–555.

    Article  PubMed  CAS  Google Scholar 

  • Stout J. T. and Caskey C. T. (1989) Hypoxanthine phosphoribosyltransferase deficiency: The Lesch Nyhan syndrome and gouty arthritis, in The Metabolic Basis of Inherited Disease, (Scriver C. R., Beaudet A. L., Sly W. S., McKusick V. A., Stanbury J. B., Wyngaarden J. B., Frederickson D. S., Goldstein J. L., and Brown M. S., eds.), McGraw Hill, New York, pp. 1007–1028.

    Google Scholar 

  • Sweetman L. (1968) Urinary and cerebrospinal fluid oxypurine levels and allopurinol metabolism in the Lesch-Nyhan syndrome. Fed. Proc. d27, 1053–1059.

    Google Scholar 

  • Sweetman L., Borden M., Kulovich S., Kaufmn I., and Nyhan W. L. (1977) Altered excretion of 5-hydroxyindoleacetic acid and glycine in patients with the Lesch-Nyhan disease, in Purine Metabolism in Man II: Regulation of Pathways and Enzyme Defects (Muller M. M., Kaiser E., and Seegmiller J. E., eds.), Plenum, New York, pp. 398–404.

    Chapter  Google Scholar 

  • Sweetman L. and Nyhan W. L. (1970) Detailed comparison of urinary excretion of purines in a patient with Lesch-Nyhan syndrome. Biochem. Med. 4, 121–134.

    Article  CAS  Google Scholar 

  • Taylor M., Goudie A. J., Mortimore S., and Wheeler T. J. (1974) Comparison between behaviours elicited by high doses of amphetamine and fenfluramine: Implications on the concept of stereotypy. Psychapharmacology 40, 249–258.

    Article  CAS  Google Scholar 

  • Towle A. G, Criswell H. E., Maynard E. H., Lauder J. M., Joh T. H., Mueller R. A., and Breese G. R. (1989) Serotonergic innervation of the rat caudate following a neonatal 6-hydroxydopamine lesion: An anatomical, biochemical and pharmacological study. Pharmacol. Biochem. Behav. 34, 367–374.

    Article  PubMed  CAS  Google Scholar 

  • Ungerstedt U. (1965) 6-hydroxydopamine induced degeneration of central monoamine neurons. Eur. J. Pharmacol. 5, 107–110.

    Article  Google Scholar 

  • Ungerstedt U. and Arbuthnott G. (1970) Quantitative recording of rotational behavior in rats after 6-OHDA lesions of the rat nigrostriatal dopamine system. Brain Res. 24,485–493.

    Article  PubMed  CAS  Google Scholar 

  • Uretsky N. J. and Iversen L. L. (1970) Effects of 6-hydroxydopamine on catecholamine neurons in the rat brain. J. Neurochem. 17, 269–278.

    Article  PubMed  CAS  Google Scholar 

  • Vaccarino F. J. and Franklin K. B. J. (1984) Opposite locomotor asymmetries elicited from the medial and lateral substantia nigra by modulation of substantia nigra dopamine receptors. Pharmacol. Biochem. Behav. 21, 73–77.

    Article  PubMed  CAS  Google Scholar 

  • Van Heeswijk P. J., Blank C. H., Seegmiller J. E., and Jacobson C. B. (1972) Preventive control of the Lesch-Nyhan syndrome. Obstetr. Gym. 40, 109–113.

    Google Scholar 

  • von Lubitz D. K. J. E., Dambrosia J. M., Kempski O., and Redmond D. J. (1988) Cyclohexyl adenosine protects against neuronal death following ischemia. Stroke 19,1133–1139.

    Article  Google Scholar 

  • Wagner G. C., Ricaurte G. A., Johanson C. E., Schuster C. R., and Seiden L. S. (1980a) Amphetamine induces depletion of dopamine and loss of dopamine uptake sites in caudate. Neurology 10, 547–550.

    Article  Google Scholar 

  • Wagner G. C., Ricaurte G. A., Seiden L. S., Schuster C. R., Miller R. J., and Westley J. (1980b) Long-lasting depletions of striatal dopamine and loss of dopamine uptake sites following repeated administration of methamphetamine. Brain Res. 181, 151–160.

    Article  PubMed  CAS  Google Scholar 

  • Waldren C. A. and Patterson D. (1979) Effects of caffeine on purine metabolism and ultraviolet light-induced lethality in cultured mammalian cells. Cancer Res. 39, 4975–4982.

    PubMed  CAS  Google Scholar 

  • Watts R. W. E. (1983) Some regulatory and integrative aspects of purine nucleotide biosynthesis and its control: An overview. Adv. Enzyme Reg. 21, 33–48.

    Article  CAS  Google Scholar 

  • Watts R. W. E., McKeran R. O., Brown E., Andrews T. M., and Griffiths M. L. (1974) Clinical and biochemical studies on treatment of Lesch-Nyhan syndrome. Arch. Dis. Childhood 49, 693–702.

    Article  CAS  Google Scholar 

  • Watts R. W. E., Spellacy E., Gibbs D. A., Allsop J., McKeran R. O.,and Slavin G. E. (1982) Clinical, post-mortem, biochemical and therapeutic observations on the Lesch-Nyhan syndrome. Q. J. Med. 201,43–78.

    Google Scholar 

  • Williams M. (1987) Purine receptors in mammalian tissues: Pharmacology and functional significance. Ann. Rev. Pharmacol. Toxicol. 17, 315–345.

    Google Scholar 

  • Willis R., Jolly D. I., Miller A. D., Plent M., Esty A., Anderson P., Jones O., Seegmiller J. E., and Friedman T. (1984) Partial phenotypic characterization of human Lesch-Nyhan (HPRT deficient) lymphoblasts with a transmissible retroviral vector. J. Biol. Chem. 259, 7842–7846.

    PubMed  CAS  Google Scholar 

  • Wilson J. M., Stout J. T., Pallela T. D., Davidson B. L., Kelley W. N., and Caskey C. T. (1986) A molecular survey of HPRT deficiency in man. J. Clin. Invest. 77, 188–195.

    Article  PubMed  CAS  Google Scholar 

  • Wilson J. M., Tarr G. E., Mahoney W. C., and Kelley W. N. (1982) Human hypoxanthine guanine phosphoribosyltransferase: Complete amino acid sequence of the erythrocyte enzyme. J. Biol. Chem. 257, 10,978–10,985; 14,830-14,834

    PubMed  CAS  Google Scholar 

  • Wilson J. M., Young A. B., and Kelley W. N. (1983) Hypoxanthine-guanine phosphoribosyltransferase deficiency: The molecular basis of the clinical syndromes. N. Engl. J. Med. 309, 900–910.

    Article  PubMed  CAS  Google Scholar 

  • Wood A. W., Becker M. A., Minna J. D., and Seegmiller J. E. (1973) Purine metabolism in normal and thioguanine-resistant neuroblastoma. Proc. Natl. Acad. Sci. USA 70, 3880–3883.

    Article  PubMed  CAS  Google Scholar 

  • Wood P. L., Kim H. S., Boyar W. C., and Hutchison A. (1988) Inhibition of nigrostriatal release of dopamine in the rat by adenosine receptor agonists: A1 receptor mediation. Neuropharmacology 26, 21–25.

    Google Scholar 

  • Wyngaarden J. B. and Ashton D. M. (1959) The regulation of activity of phosphoribosylpyrophosphate amidotransferase by purine ribonucleotides: A potential feedback control of purine biosynthesis. J. Biol. Chem. 234, 1492–1505.

    PubMed  CAS  Google Scholar 

  • Wyngaarden J. B. and Kelley W. N. (1983) Gout, in The Metabolic Basis of Inherited Disease (Stanbury J. B., Wyngaarden J. B., Frederickson D. S., Goldstein J. L., and Brown M. S., eds.), McGraw Hill, New York, 1101–1114.

    Google Scholar 

  • Yang T. P., Patel P. I., Chinault A. C., Stout J. T,, Jackson L. G., Hildebrand S. M., and Caskey C. T. (1984) Molecular evidence for new mutation in the HPRT locus in Lesch-Nyhan patients. Nature 310, 412–414.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Psychiatry and Biology, McGill University, Montreal, Québec, Canada

    Roberta M. Palmour

Authors
  1. Roberta M. Palmour
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Saskatchewan, Saskatoon, Canada

    Alan A. Boulton

  2. University of Alberta, Edmonton, Canada

    Glen B. Baker

  3. University of Montreal, Montreal, Canada

    Roger F. Butterworth

Rights and permissions

Reprints and permissions

Copyright information

© 1992 The Humana Press Inc.

About this protocol

Cite this protocol

Palmour, R.M. (1992). Animal Models for Lesch-Nyhan Disease. In: Boulton, A.A., Baker, G.B., Butterworth, R.F. (eds) Animal Models of Neurological Disease, I. Neuromethods, vol 21. Humana Press, Totowa, NJ. https://doi.org/10.1385/0-89603-208-6:295

Download citation

  • DOI: https://doi.org/10.1385/0-89603-208-6:295

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-0-89603-208-8

  • Online ISBN: 978-1-59259-626-3

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation