| First Author | Champigny MJ | Year | 2009 |
| Journal | Mol Genet Metab | Volume | 97 |
| Issue | 1 | Pages | 43-52 |
| PubMed ID | 19217813 | Mgi Jnum | J:147881 |
| Mgi Id | MGI:3842864 | Doi | 10.1016/j.ymgme.2009.01.004 |
| Citation | Champigny MJ, et al. (2009) A point mutation in the neu1 promoter recruits an ectopic repressor, Nkx3.2 and results in a mouse model of sialidase deficiency. Mol Genet Metab 97(1):43-52 |
| abstractText | SM/J is an inbred mouse strain with a complex phenotype including small body size, impaired immune response and a tissue-specific sialidase deficiency. We identified a regulatory mutation, (-519G-->A) within the neu1 promoter which in reporter assays resulted in significantly reduced transcription. This mutation generates a consensus binding site for Nkx3 family transcription repressors. Recombinant Nkx3.2 bound strongly to and preferentially repressed transcription of the mutant promoter. This tissue-specific deficiency results in a retarded immune response and modulates leukocyte recruitment. Examination of the hepatic microcirculation in mutant mice revealed increased rolling and decreased adhesion of leukocytes. Our findings support a significant role for lysosomal sialidase in inflammation and highlight the significance of repressor-recruitment in genetic disease. |
