References
Query Results -- Details
MGI Accession ID: MGI:3842864
J Number: J:147881
Other Accession IDs:
Title: A point mutation in the neu1 promoter recruits an ectopic repressor, Nkx3.2 and results in a mouse model of sialidase deficiency.
Authors: Champigny MJ; Mitchell M; Fox-Robichaud A; Trigatti BL; Igdoura SA
Journal: Mol Genet Metab
Volume: 97
Issue: 1
Date: 2009 May
Year: 2009
Pages: 43-52
Review Status: Peer Reviewed
Abstract:
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.
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