Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.1 (tyrosinase)
 9,065 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Albinism in laboratory mammals is equivalent to human tyrosinase-negative oculocutaneous albinism, and thus the result of recessive mutation in the structural locus for tyrosinase (TYR), which prevents melanin biosynthesis. In the mouse, eight mutant alleles are now known at this locus, with differing effects on eye colour and on the degree of reduction in eumelanin and phaeomelanin pigmentation. Three of these alleles, namely chinchilla, himalayan (acromelanistic) and albino (c) itself, have also been recognized in a number of other species but only albino has been identified in man so far. The himalayan allele (equivalent to Siamese in the cat) is of particular interest because it converts tyrosinase into a thermolabile form, with greater production of melanin in colder areas of the body. The optic track misrouting found in human albinos also occurs in albino alleles in other mammals, which may also show reduced activity and stress responses. The TYR locus is on human chromosome 11, which now has at least 11 loci with homologues on mouse 7. However, their order is markedly different in the two species. For instance, c and Hbb (beta-globin), which are closely linked in mouse, rabbit, cat etc., are far apart on human 11q and 11p respectively. Moreover, some loci (e.g., Fes and Mod-2) which are close to c in the mouse appear to be on human chromosomes other than 11. This extensive chromosomal restructuring in mammalian evolution means that the effects of human albino deletions may differ greatly from those studied in the mouse, which are associated with defects of kidney, liver and thymus. Tyrosinase-positive albinos or near-albinos are known at a number of loci in mice and other mammals. They are the result of the absence or inhibition of melanocytes in the affected areas, so that no melanin is produced. In general they are associated with pathological pleiotropisms which may lead to anaemia, inner ear defects, megacolon, neurological effects, skeletal defects, microphthalmia, osteopetrosis, spina bifida, sterility and so on. Homologies between these and human loci affecting pigmentation are now being discovered.
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PMID:Comparative genetics of albinism. 212 67

The endothelin receptor B gene (Ednrb) encodes a G-protein-coupled receptor that is expressed in a variety of cell types and is specifically required for the development of neural crest-derived melanocytes and enteric ganglia. In humans, mutations in this gene are associated with Waardenburg-Shah syndrome, a disorder characterized by pigmentation defects, deafness and megacolon. To address the question of whether melanocyte development depends entirely on a cell-autonomous action of Ednrb, we performed a series of tissue recombination experiments in vitro, using neural crest cell cultures from mouse embryos carrying a novel Ednrb-null allele characterized by the insertion of a lacZ marker gene. The results show that Ednrb is not required for the generation of early neural crest-derived melanoblasts but is required for the expression of the differentiation marker tyrosinase. Tyrosinase expression can be rescued, however, by the addition of Ednrb wild-type neural tubes. These Ednrb wild-type neural tubes need not be capable of generating melanocytes themselves, but must be capable of providing KIT ligand, the cognate ligand for the tyrosine kinase receptor KIT. In fact, soluble KIT ligand is sufficient to induce tyrosinase expression in Ednrb-deficient cultures. Nevertheless, these tyrosinase-expressing, Ednrb-deficient cells do not develop to terminally differentiated, pigmented melanocytes. Pigmentation can be induced, however, by treatment with tetradecanoyl phorbol acetate, which mimics EDNRB signaling, but not by treatment with endothelin 1, which stimulates the paralogous receptor EDNRA. The results suggest that Ednrb plays a significant role during melanocyte differentiation and effects melanocyte development by both cell non-autonomous and cell-autonomous signaling mechanisms.
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PMID:Cell-autonomous and cell non-autonomous signaling through endothelin receptor B during melanocyte development. 1520 Dec 17