LINEAGE-ASSOCIATED IRON OVERLOAD IN CAPTIVE FEMALE AMARGOSA VOLES (MICROTUS CALIFORNICUS SCIRPENSIS).

Within 1 yr, two cases of iron storage disease (hemochromatosis) were identified in a breeding colony of endangered Amargosa voles (Microtus californicus scirpensis). This study was designed to investigate the extent of excessive hepatic iron accumulation (iron overload with or without tissue damage) in the colony and identify risk factors such as age, sex, parity, lineage, diet, or housing that could influence management decisions for a population meant to propagate a vanishing species. The two affected voles had periportal to panlobular hepatocellular and Kupffer cell Prussian blue-positive pigment accumulation associated with hepatocellular degeneration and necrosis. By mass spectroscopy, hepatic iron content in the two affected voles was 34,000 and 6,100 parts per million (ppm) compared with 6,800 and 400 ppm in two unaffected voles. To determine the prevalence and identify risk factors, a study set of 45 voles from the pathology archives was selected within representative age groups and between sexes. The paraffin-embedded liver from study set voles was stained with Prussian blue for ferric iron. Prussian blue-positive staining was semiquantitatively scored and quantified using automated image analysis of binary pixels per region of interest. Four additional voles with excessive hepatic iron accumulation were identified within the study set. Age, diet, and types of housing were not risk factors, but female sex and lineage were risk factors. All six voles with elevated hepatic iron as measured by digital analysis or mass spectroscopy or both were female. Excluding affected voles, females had a significantly higher hepatic Prussian blue-positive signal than males. No association was identified between hepatic Prussian blue-positive signal and parity. Pedigree analysis revealed that five of six voles with elevated hepatic Prussian blue-positive signal were related to a single male founder (identification 4585). Excessive hepatic iron accumulation in this captive Amargosa vole colony is, thus, associated with female sex and was potentially heritable.