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Could you send me the "metalloproteinase" file? Thank you for your time.

Kathleen

[ ] Walsh: metallothionein inhibition: metalloproteinase, glutathione-S-transferase

MT = metallothionein TIMPs = tissue inhibitors of MPs gshST = glutathione-S-transferase Woody e-penned that "The metalloproteinase is a MT modulator. It is apparently coded on the X Chromosome right next to the locus for night blindness. Might want to check that out a little." Medline quickly revealed that humans have a goodly number of metalloproteinase genes (on a number of chromosomes), and that the first such gene discovered (way back in 1986) is indeed very close to several genes relating to night blindness, retinitis pigmentosa, etc. If Walsh's "low metallothionein" findings are replicated and "generally true", then there seem to be at least two major candidates for inducing low MT: the TIMP family of genes, and the gshST family of genes. Furthermore, irregularities and alleles of gshST genes and of TIMP genes are already described and provide a basis for much interindividual variation, especially when manifested through a complex pathway such as MT gene-expression and the environmental variables influenced by MT levels. An attachment herewith contains abstracts (a) about chromosomal locations of TIMP genes and, to some extent, their disease associations, and ( about an X-chromosome TIMP implicated in night blindness, a factoid with possible relevance to Megson's findings. The attachment is 14 pages in length, contains some gems, and lots of other info for persons wanting an overview of genomic TIMP locations. As I was sending the attachment, I saw that it is appx 500k, so I cancelled that post. If someone wants the file, write me off list and request the "metalloproteinase" file. Here is several tidbits from the attachment: Genomics 1994 May 15;21(2):337-43 A 1.8-Mb YAC contig in Xp11.23: identification of CpG islands and physical mapping of CA repeats in a region of high gene density. MP, Nemeth AH, L, Raut CP, Weissenbach J, Davies KE Institute of Molecular Medicine, Radcliffe Hospital, Headington, Oxford. The genes ARAF1, SYN1, TIMP, and PFC are clustered within 70 kb of one another, and, as reported in the accompanying paper (J. Knight et al., 1994, Genomics 21: 180-187), at least four more genes map within 400 kb: a cluster of Kruppel-type zinc finger genes (including ZNF21, ZNF41, and ZNF81) and ELK-1, a member of the ets oncogene superfamily. This gene-rich region is of particular interest because of the large number of disease genes mapping to Xp11.23: at least three eye diseases (retinitis pigmentosa type 2, congenital stationary night blindness CSNB1, and Aland Island eye disease), Wiskott-Aldrich syndrome, X-linked nephrolithiasis, and a translocation breakpoint associated with synovial sarcoma... 11: Am J Hum Genet 1993 Jan;52(1):71-7 Manifestations of X-linked congenital stationary night blindness in three daughters of an affected male: demonstration of homozygosity. Bech-Hansen NT, Pearce WG Department of Paediatrics, Alberta Children's Hospital, Calgary, Canada. X-linked congenital stationary night blindness (CSNB1) is a hereditary retinal disorder in which clinical features in affected males usually include myopia, nystagmus, and impaired visual acuity. Electroretinography demonstrates a marked reduction in b-wave amplitude. In the study of a large Mennonite family with CSNB1, three of five sisters in one sibship were found to have manifestations of CSNB1. All the sons of these three sisters were affected. Each of the two nonmanifesting sisters had at least one unaffected son. Analysis of Xp markers in the region Xp21.1-Xp11.22 showed that the two sisters who were unaffected had inherited the same maternal X chromosome (i.e., M2). Two of the daughters who manifested with CSNB had inherited the other maternal X chromosome (M1). The third manifesting sister inherited a recombinant X chromosome with a crossover between TIMP and DXS255, which suggests that the CSNB1 locus lies proximal to TIMP. One of the affected daughters' sons had inherited the maternal M1 X chromosome, a finding consistent with that chromosome carrying a mutant CSNB gene; the other affected sons inherited the grandfather's X chromosome (i.e., P). Molecular analysis of DNA from three sisters with manifestations of CSNB is consistent with their being homozygous at the CSNB1 locus and with their mother being a carrier of CSNB1. 13: Genomics 1992 Apr;12(4):632-8 Physical linkage of the A-raf-1, properdin, synapsin I, and TIMP genes on the human and mouse X chromosomes. Derry JM, Barnard PJ MRC Molecular Neurobiology Unit, MRC Centre, Cambridge, United Kingdom. Genes encoding the neuron-specific phosphoprotein synapsin I (SYN1), the glycoprotein tissue inhibitor of metalloproteinases (TIMP), the proto-oncogene A-raf-1 (ARAF1), and properdin (PFC), a positive regulator of the alternative pathway of human complement, lie within a conserved synteny encompassing the proximal short arm of the human X chromosome (Xp21.1-p11) and the centromeric end of the mouse X chromosome (A1-A5). We have used a mouse interspecific cross to demonstrate genetic linkage of Syn-1, Timp, and Araf and also show physical linkage, with Timp lying only 10 kb from Araf, within an intron of the Syn-1 gene. Detailed restriction mapping shows that Timp is transcribed in the same direction as Araf but in the opposite direction to the Syn-1 gene. Analysis of the corresponding region of the human X chromosome indicates a similar arrangement and in addition shows that the properdin gene lies within 5 kb of the 5' end of the synapsin I gene. Exciting "stuff"!