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Prior studies have shown enhanced ENaC \u03b3 subunit proteolysis and Na\n                    <jats:sup>+<\/jats:sup>\n                    and fluid retention in 129S1\/SvImJ mice treated with doxorubicin. We examined whether 129S2\/SvPas mice could be used to study doxorubicin\u2010induced proteinuria. 129S2\/SvPas mice treated with 18\u2009\u03bcg\/g doxorubicin exhibited significantly reduced urinary albumin\/creatinine compared to that described for 129S1\/SvImJ mice. Proteolytic processing of ENaC's \u03b3 subunit and sensitivity of urinary Na\n                    <jats:sup>+<\/jats:sup>\n                    and K\n                    <jats:sup>+<\/jats:sup>\n                    to the ENaC blocker, benzamil, were not enhanced by doxorubicin. Differences in the DNA repair enzyme, DNA\u2010activated protein kinase (DNA\u2010PKcs) may contribute to the difference in doxorubicin susceptibility of 129S2\/SvPas and 129S1\/SvImJ mice. Sequencing of the\n                    <jats:italic>Prkdc<\/jats:italic>\n                    , encoding DNA\u2010PKcs, showed that 129S2\/SvPas mice lack a polymorphism (Arg2140Cys) that has previously been implicated in doxorubicin sensitivity in 129S1\/SvImJ mice. The status of this polymorphism in various experimental mouse strains, and therefore implications for studying doxorubicin\u2010induced proteinuria, is discussed.\n                  <\/jats:p>","DOI":"10.14814\/phy2.70667","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T07:30:26Z","timestamp":1765265426000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Resistance to doxorubicin\u2010induced proteinuria and proteolytic activation of\n                    <scp>ENaC<\/scp>\n                    in\n                    <scp>129S2<\/scp>\n                    \/\n                    <scp>SvPas<\/scp>\n                    mice"],"prefix":"10.14814","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1491-4869","authenticated-orcid":false,"given":"Evan C.","family":"Ray","sequence":"first","affiliation":[{"name":"Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivy","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niloofar","family":"Momenzadeh","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kennedy","family":"Szekely","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allison L.","family":"Marciszyn","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tracey","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew J.","family":"Nickerson","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2413-5415","authenticated-orcid":false,"given":"Thomas R.","family":"Kleyman","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Cell Biology University of Pittsburgh  Pittsburgh Pennsylvania USA"},{"name":"Department of Pharmacology and Chemical Biology University of Pittsburgh  Pittsburgh Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.13811"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfu402"},{"key":"e_1_2_11_4_1","first-page":"1","article-title":"Proteolytic activation of the epithelial sodium channel (ENaC) by factor VII activating protease (FSAP) and its relevance for sodium retention in nephrotic mice","volume":"474","author":"Artunc F.","year":"2022","journal-title":"Pfl\u00fcgers Archiv \/ European Journal of Physiology"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00032.2008"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-016-0110-x"},{"key":"e_1_2_11_7_1","article-title":"Induction of nephrotic syndrome in mice by retrobulbar injection of doxorubicin and prevention of volume retention by sustained release aprotinin","volume":"6","author":"Bohnert B. 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