@article{Thomas B. Bartnikas_Andrea U. Steinbicker_Dean R. Campagna_Sherika Blevins_Lanette S. Woodward_Carolina Herrera_Kenneth D. Bloch_Monica J. Justice_Mark D. Fleming_2013, place={Pavia, Italy}, title={Identification and characterization of a novel murine allele of Tmprss6}, volume={98}, url={https://haematologica.org/article/view/6684}, DOI={10.3324/haematol.2012.074617}, abstractNote={Mutagenesis screens can establish mouse models of utility for the study of critical biological processes such as iron metabolism. Such screens can produce mutations in novel genes or establish novel alleles of known genes, both of which can be useful tools for study. In order to identify genes of relevance to hematologic as well as other phenotypes, we performed N-ethyl-N-nitrosourea mutagenesis in C57BL/6J mice. An anemic mouse was identified and a putative mutation was characterized by mapping, sequencing and <em>in vitro</em> activity analysis. The mouse strain was backcrossed for ten generations then phenotypically characterized with respect to a previously established null mouse strain. Potential modifying loci were identified by quantitative trait locus analysis. Mapping and sequencing in an anemic mouse termed <em>hem8</em> identified an I286F substitution in Tmprss6, a serine protease essential for iron metabolism; this substitution impaired <em>in vitro</em> protease activity. After backcrossing to C57BL6/J for ten generations, the <em>hem8</em><sup>−/−</sup> strain exhibited a phenotype similar in some but not all aspects to that of <em>Tmprss6</em><sup>−/−</sup> mice. The hem8 and Tmprss6-null mutations were allelic. Both <em>hem8</em><sup>−/−</sup> and <em>Tmprss6</em><sup>−/−</sup> mice responded similarly to pharmacological modulators of bone morphogenetic protein signaling, a key regulator of iron metabolism. Quantitative trait locus analysis in the <em>hem8</em> strain identified potential modifying loci on chromosomes 2, 4, 7 and 10. In conclusion, the <em>hem8</em> mouse model carries a novel allele of <em>Tmprss6</em&gt;. Potential uses for this strain in the study of iron metabolism are discussed.}, number={6}, journal={Haematologica}, author={Thomas B. Bartnikas and Andrea U. Steinbicker and Dean R. Campagna and Sherika Blevins and Lanette S. Woodward and Carolina Herrera and Kenneth D. Bloch and Monica J. Justice and Mark D. Fleming}, year={2013}, month={May}, pages={854-861} }