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International Journal of Experimental Diabesity Research logoLink to International Journal of Experimental Diabesity Research
. 2003;4(1):35–44. doi: 10.1080/15438600303733

Development of Type 1 Diabetes in Wild Bank Voles Associated With Islet Autoantibodies and the Novel Ljungan Virus

Bo Niklasson 1, Knud E Heller 2, Bryan Schønecker 2, Mogens Bildsøe 2, Terri Daniels 3, Christiane S Hampe 3, Per Widlund 3, William T Simonson 3, Jonathan B Schaefer 3, Terri Daniels 3, Elizabeth Rutledge 3, Lynn Bekris 3, A Michael Lindberg 4, Susanne Johansson 4, Eva Örtqvist 5, Bengt Persson 5, Åke Lernmark 3,
PMCID: PMC2480497  PMID: 12745669

Abstract

Wild bank voles (Clethrionomys glareolus) may develop diabetes in laboratory captivity. The aim of this study was to test whether bank voles develop type 1 diabetes in association with Ljungan virus. Two groups of bank voles were analyzed for diabetes, pancreas histology, autoantibodies to glutamic acid decarboxylase (GAD65), IA-2, and insulin by standardized radioligand-binding assays as well as antibodies to in vitro transcribed and translated Ljungan virus antigens. Group A represented 101 trapped bank voles, which were screened for diabetes when euthanized within 24 hours of capture. Group B represented 67 bank voles, which were trapped and kept in the laboratory for 1 month before being euthanized. Group A bank voles did not have diabetes. Bank voles in group B (22/67; 33%) developed diabetes due to specific lysis of pancreatic islet beta cells. Compared to nondiabetic group B bank voles, diabetic animals had increased levels of GAD65 (P < .0001), IA-2 (P < .0001), and insulin (P = .03) autoantibodies. Affected islets stained positive for Ljungan virus, a novel picorna virus isolated from bank voles. Ljungan virus inoculation of nondiabetic wild bank voles induced beta-cell lysis. Compared to group A bank voles, Ljungan virus antibodies were increased in both nondiabetic (P < .0001) and diabetic (P = .0015) group B bank voles. Levels of Ljungan virus antibodies were also increased in young age at onset of newly diagnosed type 1 diabetes in children (P < .01). These findings support the hypothesis that the development of type 1 diabetes in captured wild bank voles is associated with Ljungan virus. It is speculated that bank voles may have a possible zoonotic role as a reservoir and vector for virus that may contribute to the incidence of type 1 diabetes in humans.

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