Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Lesch-Nyhan syndrome (LNS) has been extensively studied from the genetic and biochemical point of view. The main characteristic of the syndrome is the self-mutilation feature, which has been poorly studied and understood. We propose a new hypothesis about the self-mutilation physiopathology, which is related to the supersensitivity of the dopaminergic D1 receptors in the neuromatrix found in the cingulum cortex region. The LNS shows an increase of uric acid levels as a result of the deficiency of hypoxanthine phosphoribosyltransferase enzyme. This increase could induce damage to dopaminergic neurons. As a consequence, a decrease in dopamine synthesis during gestation and the early postnatal period could occur, producing a functional dopaminergic denervation of the D1 receptors, located on the prefrontal cortex, specifically in the cingulum bundle projections. This phenomenon could induce a codification disturbance in the 'genetic body' of the neuromatrix, that could be expressed functionally as anosognosia, giving rise to self-mutilation. We suggest that this self-mutilation is a pain consciousness problem.
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PMID:Self-mutilation in the Lesch-Nyhan syndrome: a corporal consciousness problem?--a new hypothesis. 948 81

The most long-lived metaphysics or view of reality in the history of Western thought is Aristotle's teleology, which reigned for almost 2,000 years. Biology was expressed in terms of function or telos, and accorded perfectly with common sense. The rise of mechanistic, Newtonian science vanquished teleological explanations. Understanding and accommodating animal telos was essential to success in animal husbandry, which involved respect for telos, and was presuppositional to our "ancient contract" with domestic animals. Telos was further abandoned with the rise of industrial agriculture, which utilized "technological fixes" to force animal into environments they were unsuited for, while continuing to be productive. Loss of husbandry and respect for telos created major issues for farm animal welfare, and forced the creation of a new ethic demanding respect for telos. As genetic engineering developed, the notion arose of modifying animals to fit their environment in order to avoid animal suffering, rather than fitting them into congenial environments. Most people do not favor changing the animals, rather than changing the conditions under which they are reared. Aesthetic appreciation of husbandry and virtue ethics militate in favor of restoring husbandry, rather than radically changing animal teloi. One, however, does not morally wrong teloi by changing them-one can only wrong individuals. In biomedical research, we do indeed inflict major pain, suffering and disease on animals. And genetic engineering seems to augment our ability to create animals to model diseases, particularly more than 3,000 known human genetic diseases. The disease, known as Lesch-Nyhan's syndrome or HPRT deficiency, which causes self-mutilation and mental retardation, provides us with a real possibility for genetically creating "animal models" of this disease, animals doomed to a life of great and unalleviable suffering. This of course creates a major moral dilemma. Perhaps one can use the very genetic engineering which creates this dilemma to ablate consciousness in such animal models, thereby escaping a moral impasse.
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PMID:Telos, conservation of welfare, and ethical issues in genetic engineering of animals. 2449 50