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Variant description |
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Mapping and Phenotype information for this QTL, its variants and associated markersJ:235239Neutrophil recruitment (NR) to sites of sterile inflammation (SI) plays a key role in tissue damage and healing potential of lesions characteristic to non-infectious inflammatory diseases. The neutrophils involvement and contribution to SI depends on its ability to respond to in vivo cell death and migrate to the site of injury. In the current study QTL harboring genetic determinants that regulate NR in SI using a murine model of chemically-induced peritonitis were mapped.NR was quantified in 16 AXB-BXA recombinant inbred strains and their progenitors, A/J (A) and C57BL/6J (B). A continuous distribution of NR was found among the strains, with parent B showing higher NR and parent A showing lower NR (3.0-fold difference, p=0.05). Within the progeny strains, a 5.5-fold difference in NR was observed between the lowest, BXA1, and the highest responders AXB19 (p<0.001).Up to 6 mice were used from each of 16 RI strains along with the parental strains, (N=80, 9-18 week old mice), to phenotype the level of NR in response to experimental SI induced by injection of the chemical irritant sodium periodate.Interval mapping software, followed by a 2.0-LOD drop-off, identified a significant QTL on Chr 12 spanning a confidence interval of 5.47 Mb (from 72.81 Mb to 78.28 Mb; LRS = 17.52, LOD = 3.8). The QTL was named Pnrq1 (peritoneal neutrophil recruitment QTL 1) (Fig 2). Pnrq1 harbors 64 genes (Table 1). The strongest candidate gene is Hif1a, encoding for HIF1, the alpha subunit of Hypoxia Inducible Factor 1, which may control early NR and survival into injured tissues during SI.Two suggestive QTL were identified; one (Pnr2) mapped to Chr 12 spanning a length of 18 Mb (from 87.0- 101.6 Mb; LRS = 11.1, LOD = 2.4) and contained 130 genes (S1 Table), the other (Pnr3) mapped to Chr 16, spanning 18.5 Mb (from 56.5-75.0 Mb) and contained 96 genes (S3 Table). |
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References |
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Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO) |
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last database update 11/19/2024 MGI 6.24 |
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