The use of perinatal 6-Hydroxydopamine to produce a rodent model of Lesch-Nyhan disease

Darin J. Knapp, George R. Breese

Research output: Chapter in Book/Report/Conference proceedingChapter

  • 3 Citations

Abstract

Lesch-Nyhan disease is a neurologically, metabolically, and behaviorally devastating condition that has eluded complete characterization and adequate treatment. While it is known that the disease is intimately associated with dysfunction of the hypoxanthine phosphoribosyltransferase 1 (HPRT1) gene that codes for an enzyme of purine metabolism (hypoxanthine-guanine phosphoribosyltransferase) and is associated with neurological, behavioral, as well as metabolic dysfunction, the mechanisms of the neurobehavioral manifestations are as yet unclear. However, discoveries over the past few decades not only have created useful novel animal models (e.g., the HPRT-deficient mouse and the serendipitously discovered perinatal 6-hydroxydopamine (6-OHDA lesion model), but also have expanded into epigenetic, genomic, and proteomic approaches to better understand the mechanisms underlying this disease. The perinatal 6-OHDA model, in addition to modeling self-injury and dopamine depletion in the clinical condition, also underscores the profound importance of development in the differential course of maladaptive progression in the face of a common/single neurotoxic insult at different ages. Recent developments from clinical and basic science efforts attest to the fact that while the disease would seem to have a simple single gene defect at its core, the manifestations of this defect are profound and unexpectedly diverse. Future efforts employing the 6-OHDA model and others in the context of the novel technologies of genome editing, chemo-and opto-genetics, epigenetics, and further studies on the mechanisms of stress-induced maladaptations in brain all hold promise in taking our understanding of this disease to the next level.

LanguageEnglish (US)
Title of host publicationCurrent Topics in Behavioral Neurosciences
PublisherSpringer Verlag
Pages265-277
Number of pages13
DOIs
StatePublished - Apr 1 2016

Publication series

NameCurrent Topics in Behavioral Neurosciences
Volume29
ISSN (Print)1866-3370
ISSN (Electronic)1866-3389

Fingerprint

Lesch-Nyhan Syndrome
Oxidopamine
Hypoxanthine Phosphoribosyltransferase
Rodentia
Epigenomics
Neurobehavioral Manifestations
Inborn Genetic Diseases
Proteomics
Dopamine
Animal Models
Technology
Wounds and Injuries
Brain
Enzymes
Genes

Keywords

  • 6-hydroxydopamine 6-OHDA
  • Animal models
  • L-DOPA
  • Lesch-Nyhan disease
  • Perinatal
  • Rats
  • Self-injurious behavior

ASJC Scopus subject areas

  • Behavioral Neuroscience

Cite this

Knapp, D. J., & Breese, G. R. (2016). The use of perinatal 6-Hydroxydopamine to produce a rodent model of Lesch-Nyhan disease. In Current Topics in Behavioral Neurosciences (pp. 265-277). (Current Topics in Behavioral Neurosciences; Vol. 29). Springer Verlag. DOI: 10.1007/7854_2016_444

The use of perinatal 6-Hydroxydopamine to produce a rodent model of Lesch-Nyhan disease. / Knapp, Darin J.; Breese, George R.

Current Topics in Behavioral Neurosciences. Springer Verlag, 2016. p. 265-277 (Current Topics in Behavioral Neurosciences; Vol. 29).

Research output: Chapter in Book/Report/Conference proceedingChapter

Knapp, DJ & Breese, GR 2016, The use of perinatal 6-Hydroxydopamine to produce a rodent model of Lesch-Nyhan disease. in Current Topics in Behavioral Neurosciences. Current Topics in Behavioral Neurosciences, vol. 29, Springer Verlag, pp. 265-277. DOI: 10.1007/7854_2016_444
Knapp DJ, Breese GR. The use of perinatal 6-Hydroxydopamine to produce a rodent model of Lesch-Nyhan disease. In Current Topics in Behavioral Neurosciences. Springer Verlag. 2016. p. 265-277. (Current Topics in Behavioral Neurosciences). Available from, DOI: 10.1007/7854_2016_444
Knapp, Darin J. ; Breese, George R./ The use of perinatal 6-Hydroxydopamine to produce a rodent model of Lesch-Nyhan disease. Current Topics in Behavioral Neurosciences. Springer Verlag, 2016. pp. 265-277 (Current Topics in Behavioral Neurosciences).
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