Isolation and characterization of bovine Nramp1 and bison Nramp1 : a major candidate gene for natural resistance to brucellosis /
The Bcg/Ity/Lsh is a major gene controlling early phases of infection with a variety of intracellular parasites in mice. The murine natural resistance associated membrane protein (Nrampl) gene has been isolated by positional cloning and subsequently confirmed as the Bcg gene by gene knock-out studie...
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| Format: | Thesis Book |
| Language: | English |
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[Place of publication not identified] :
[publisher not identified] ;
1996.
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| Subjects: | |
| Online Access: | http://proxy.library.tamu.edu/login?url=http://proquest.umi.com/pqdweb?did=743266301&sid=1&Fmt=2&clientId=2945&RQT=309&VName=PQD |
| Summary: | The Bcg/Ity/Lsh is a major gene controlling early phases of infection with a variety of intracellular parasites in mice. The murine natural resistance associated membrane protein (Nrampl) gene has been isolated by positional cloning and subsequently confirmed as the Bcg gene by gene knock-out studies. Analysis of both bovine and bison CDNA homologs of murine Nrampl predicted mainly identical integral membrane proteins composed of 548 amino-acids with 12 hydrophobic domains, an NH2 terminus SH3-binding domain and a conserved consensus nitrate/nitrite transport motif. Northern blotting indicated that bovine NRAMPI is primarily expressed in macrophages, spleen and lung. Also a higher expression of bovine NRAMPI was observed in resting and Brucella challenged macrophages of resistant cattle compared to those of susceptible animals. Bovine NRAMP1 has been mapped to Bos taurus autosome (BTA) 2 within syntenic loci conserved on HSA 2q and MMU 1 and is contained on a 90 kb DNA fragment which also contains at least a portion of the bovine VIL gene. Single stranded conformational analysis revealed a highly significant association of bovine NRAMPI with natural resistance to brucellosis in cattle. An association of bison NRAMP1 with natural resistance to brucellosis in bison has been observed. Together, these data imply that bovine and bison NRAMPI are the major candidate genes for controlling natural disease resistance to brucellosis. Bovine NRAMPl spans approximately 12 kb of genomic DNA with no TATA and CAAT boxes found in the 1484 bp 5' flanking region. However, a 250 bp fragment upstream of the transcription start site, which contains several consensus cis-acting elements specifically mediating the macrophage and cytokine gene expression, was conserved among bovine, human and murine Nrampl. These observations suggest that this segment may serve an essential promoter function for Nrampl expression. An alanine-217 to valine-217 and a glycine 542 deletion were found in two susceptible cattle, respectively. Additionally, identification of a 93 bp fragment containing T1782 in the R cattle and G1782 in S animals may be critical for binding to an unknown nuclear protein(s) from the R activated macrophages. |
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| Item Description: | Vita. "Major Subject: Veterinary Microbiology". |
| Physical Description: | xii, 138 leaves : illustrations ; 28 cm. Issued also on microfiche from University Microfilms Inc. |
| Bibliography: | Includes bibliographical references. |