TIMP-1 expression is increased in X-linked progressive retinal atrophy despite its exclusion as a candidate gene.
Gene
; 225(1-2): 67-75, 1998 Dec 28.
Article
em En
| MEDLINE
| ID: mdl-9931441
ABSTRACT
X-linked progressive retinal atrophy (XLPRA) is the only known natural animal model for X-linked retinitis pigmentosa (XLRP), a blinding disorder in man. The tissue inhibitor metalloproteinase 1 gene (TIMP-1), present in close proximity to one of the two XLRP loci, was tested as a candidate for XLPRA, by first characterizing the cDNA and gene from a normal dog. The cloned canine TIMP-1 cDNA is predicted to encode a protein of 207 amino acids with 66-83% identity in the deduced aa sequence with homologous mammalian genes. No sequence difference in the coding sequence of TIMP-1 was observed between normal and XLPRA-affected dogs. TIMP-1 was found to be expressed in all of the canine tissues examined by reverse transcription and polymerase chain reaction. The canine TIMP-1 spans 3.5kb and is interrupted by five introns with sizes comparable to those observed in the human and mouse homologues of the gene. The proximal promoter region of canine TIMP-1 contains sequence motifs shown to have regulatory significance in transcription of human TIMP-1. Linkage analysis between XLPRA and TIMP-1 using a newly identified intragenic polymorphism identified recombinants, which conclusively excluded the gene as a candidate for the disease. TIMP-1 is overexpressed several months before retinal degeneration is histologically evident in XLPRA dogs, implying that alterations in interphotoreceptor matrix composition precede retinal degeneration by a significant time period.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Degeneração Retiniana
/
Cromossomo X
/
Inibidor Tecidual de Metaloproteinase-1
/
Doenças do Cão
/
Genes
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Gene
Ano de publicação:
1998
Tipo de documento:
Article
País de afiliação:
Estados Unidos