Interleukin-1 ? and ? genes: linkage on chromosome 2 in the mouse

D’Eustachio, Peter; Jadidi, Shirin; Fuhlbrigge, Robert C.; Gray, Patrick W.; Chaplin, David

doi:10.1007/bf00343701

Cited by 62 publications

(18 citation statements)

References 26 publications

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“…(i) Prn-p. Three Prn-p cDNA probes were used. Both a 2-kilobase (kb) insert from a hamster PrP cDNA clone (44) and a 900-base-pair (bp) EcoRI fragment from subclone 13 of a mouse cDNA (11) (20) and the Klenow fragment of DNA polymerase I (61).…”

Section: Methodsmentioning

confidence: 99%

Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time.

Carlson¹,

Goodman²,

Lovett³

et al. 1988

Mol. Cell. Biol.

152

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The mouse prion protein (PrP) gene (Prn-p), which encodes the only macromolecule that has been identified in scrapie prions, is tightly linked or identical to a gene (Prn-i) that controls the duration of the scrapie incubation period in mice. Constellations of restriction fragment length polymorphisms distinguish haplotypes a to f of Prn-p. The Prn-pb allele encodes a PrP that differs in sequence from those encoded by the other haplotypes and, in inbred mouse strains, correlates with long scrapie incubation time (Westaway et al., Cell 51: 651-662, 1987). In segregating crosses of mice, we identified rare individuals with a divergent scrapie incubation time phenotype and Prn-p genotype, but progeny testing to demonstrate meiotic recombination was not possible because scrapie is a lethal disease. Crosses involving the a, d, and e haplotypes demonstrated that genes unlinked to Prn-p could modulate scrapie incubation time and that there were only two alleles of Prn-i among the mouse strains tested. All inbred strains of mice that had the Prnb haplotype were probably direct descendants of the I/LnJ progenitors. We established the linkage relationship between the prion gene complex (Prn) and other chromosome 2 genes; the gene order, proximal to distal, is B2m-II-1a-Prn-Itp-A. Recombination suppression in the B2m-Prn-p interval occurred during the crosses involved in transferring the I/LnJ Prnb complex into a C57BL/6J background. Transmission ratio distortion by Prna/Prnb heterozygous males was also observed in the same crosses. These phenomena, together with the founder effect, would favor apparent linkage disequilibrium between Prn-p and Prn-i. Therefore, transmission genetics may underestimate the number of genes in Prn.

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Section: Methodsmentioning

confidence: 99%

Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time.

Carlson¹,

Goodman²,

Lovett³

et al. 1988

Mol. Cell. Biol.

152

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“…There are two proIL-1 genes (proIL-lco and proIL-113) coding for distinct proteins which are observed in many different species (7,18). The two proIL-1 genes are located on human chromosome 2 (11,30,48) and show a high conservation of exon/intron structure (7). IL-1 has a variety of biological activities on a wide range of tissues (see reference 13 for a review).…”

mentioning

confidence: 99%

The human prointerleukin 1 beta gene requires DNA sequences both proximal and distal to the transcription start site for tissue-specific induction.

Shirakawa¹,

Saito²,

Bonagura³

et al. 1993

Mol. Cell. Biol.

164

165

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In these studies, we have identified DNA sequences and specific protein interactions necessary for transcriptional regulation of the human prointerleukin 113 (proIL-i1i) gene. A cell-type-independent lipopolysaccharide (LPS)-responsive enhancer element located between -3757 and -2729 bp upstream from the transcription start site (cap site) consisted of at least six discrete subregions which were essential to the maximal induction by LPS in transfected monocytes. The enhancer also appeared to mediate phorbol myristate acetate induction in monocytes and IL-1 responsiveness in fibroblasts. Deletion and base substitution mutations along with DNA binding studies demonstrated that the enhancer contained a minimum of three functional protein binding sequences, two of which appeared to be important for gene induction. One of the essential proteins which bound to the enhancer was similar or identical to members of the C/EBP family of transcription factors required for both IL-1-and LPS-specific induction of the IL-6 gene (i.e., the NF-IL6 proteins). When ligated to the proIL-1l3 cap site-proximal region (located between -131 to +12), both the proIL-1,3 and the simian virus 40 enhancer elements functioned more efficiently in monocytes than in HeLa cells, which are not normally competent for IL-11 expression. When ligated to the murine c-fos promoter, however, the proIL-1j3 enhancer was inducible in phorbol myristate acetate-stimulated HeLa cells, suggesting the existence of a proIL-1,3 promoter-proximal requirement for tissue specificity.Interleukin 11 (IL-113), a 17-kDa cytokine involved in inflammatory and immunological processes, is produced by activated monocytes/macrophages, fibroblasts, endothelial cells, and other cell types. The IL-1 proteins are translated as larger 31-kDa precursors (proIL-1) which are extracellularly processed into smaller 17-kDa forms (mature IL-1) (4, 20). There are two proIL-1 genes (proIL-lco and proIL-113) coding for distinct proteins which are observed in many different species (7, 18). The two proIL-1 genes are located on human chromosome 2 (11, 30, 48) and show a high conservation of exon/intron structure (7). IL-1 has a variety of biological activities on a wide range of tissues (see reference 13 for a review). For example, IL-1 induces the production of inflammatory mediators, proteolytic enzymes, and other cytokines that are involved in the joint destruction and inflammation of rheumatoid arthritis (29). IL-1 also modifies connective tissue and bone metabolism through the induction and type switch of collagen and the induction of bone resorption (21).The proIL-113 gene is normally not transcribed in competent cells until activated by stimuli such as lipopolysaccharide (LPS) or phorbol 12-myristate acetate (PMA) or by 17-kDa IL-11 protein (9,13,14 with LPS, IL-1P mRNA is rapidly and transiently transcribed in the absence of protein synthesis (15), suggesting the activation of preexisting transcription factors. Our previous studies revealed the importance of promoter sequences immediat...

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“…A DNA probe, corresponding to a 0.2-kb restriction fragment unique to the region 3' to the breakpoint on the mutant 7.5-kb fragment (Fig. 3B), was hybridized to DNA from somatic cell hybrids containing, along with other mouse chromosomes, either both chromosomes 2 and 17 (hybrid line BEM 1-4) or just mouse chromosome 17 (hybrid line R44-1) (23). Results showed that the probes hybridized to chromosome 2 but not to chromosome 17 (data not shown).…”

mentioning

confidence: 99%

Molecular and genetic characterization of a radiation-induced structural rearrangement in mouse chromosome 2 causing mutations at the limb deformity and agouti loci.

Woychik

Generoso

Russell

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

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Molecular characterization of mutations in the mouse, particularly those involving agent-induced major structural alterations, is proving to be useful for correlating the structure and expression of individual genes with their function in the whole organism. Here we present the characterization of a radiation-induced mutation that simultaneously generated distinct alleles of both the limb deformity (ld) and agouti (a) loci, two developmentally important regions of chromosome 2 normally separated by 20 centimorgans. Cytogenetic analysis revealed that an interstitial segment of chromosome 17 (17B- 17C; or, possibly, 17A2-17B) had been translocated into the distal end of chromosome 2, resulting in a smaller-than-normal chromosome 17 (designated 17del) and a larger form of chromosome 2 (designated 2(17). Additionally, a large interstitial segment of the 2(17) chromosome, immediately adjacent and proximal to the insertion site, did not match bands 2E4-2H1 at corresponding positions on a normal chromosome 2. Molecular analysis detected a DNA rearrangement in which a portion of the ld locus was joined to sequences normally tightly linked to the a locus. This result, along with the genetic and cytogenetic data, suggests that the alleles of ld and a in this radiation-induced mutation, designated ldIn2 and ajIn2, were associated with DNA breaks caused by an inversion of an interstitial segment in the 2(17) chromosome.

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Interleukin-1 ? and ? genes: linkage on chromosome 2 in the mouse

Cited by 62 publications

References 26 publications

Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time.

Genetics and polymorphism of the mouse prion gene complex: control of scrapie incubation time.

The human prointerleukin 1 beta gene requires DNA sequences both proximal and distal to the transcription start site for tissue-specific induction.

Molecular and genetic characterization of a radiation-induced structural rearrangement in mouse chromosome 2 causing mutations at the limb deformity and agouti loci.

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