Showing papers by "Simon A. Forbes published in 1999"
TL;DR: The mouse men1 gene and the basis of alternative transcripts have been defined, and these will help to facilitate studies of a mouse model.
Abstract: The murine homolog of the multiple endocrine neoplasia type 1 (MEN1) gene (men1), which in humans is associated with tumors of the parathyroids, pancreas, and pituitary, has been characterized by isolating 27 clones from a mouse embryonic stem cell cDNA library The insert sizes ranged from 600–2500 bp, and sequence analysis identified a 1833 bp open reading frame encoding a 611 amino acid protein In addition, two clones contained an unspliced intron 1, and another two clones contained 20–29 bp of an upstream sequence, which suggested the presence of an alternate exon 1 This was supported by an analysis of the homologous human sequence The mouse and human coding regions had 89% and 96% identity of the nucleotide and amino acid sequences, respectively Investigation of clones isolated from a 129ola mouse genomic library, revealed the men1 gene to consist of 10 exons that spanned ∼6 kb Northern blot analysis demonstrated the ubiquitous expression of 29 kb and 34 kb transcripts in mouse adult tissues and embryos from 7 days DNA sequence analysis of the larger 34 kb transcript revealed it to result from a retention of intron 1 In situ hybridization confirmed an early ubiquitous expression in whole mount mouse embryos and adult tissues, but in the latter, different levels of cellular expression were observed, eg, men1 expression was higher in testicular Sertoli cells than in germ cells Thus, the mouse men1 gene and the basis of alternative transcripts have been defined, and these will help to facilitate studies of a mouse model
57 citations
TL;DR: A Portuguese kindred with autosomal dominant isolated primary hyperparathyroidism that was associated with parathyroid adenomas and carcinomas was investigated and the chromosomal location of this gene was determined, designated HPTPort, to chromosome 1q22‐q31.
Abstract: A Portuguese kindred with autosomal dominant isolated primary hyperparathyroidism (HPT) that was associated with parathyroid adenomas and carcinomas was investigated with the aim of determining the chromosomal location of this gene, designated HPTPort. Leukocyte DNA from 9 affected and 16 unaffected members and 7 parathyroid tumors from 4 patients was used in comparative genomic hybridization (CGH), tumor loss of heterozygosity (LOH), and family linkage studies. The CGH studies revealed abnormalities of chromosomes 1 and 13, and the results of LOH studies were consistent with the involvements of tumor suppressor genes from these regions. Family segregation studies mapped HPTPort to chromosome 1q22-q31 by establishing linkage with eight loci (D1S254, D1S222, D1S202, D1S238, D1S428, D1S2877, D1S422, and D1S412) (peak two-point LOD scores = 3. 46–5.14 at 0% recombination), and defined the location of HPT Port to a 21 cM region flanked centromerically by D1S215 and telomerically by D1S306. Thus, HPTPort has been mapped to chromosome 1q22-q31, and a characterization of this gene will help to elucidate further the mechanisms that are involved in the development of parathyroid tumors.
47 citations