Veterinary Parasitology 103 (2002) 315–321 Mice lacking the gene for inducible or endothelial nitric oxide are resistant to sporocyst induced Sarcocystis neurona infections Alexa C. Rosypal a , David S. Lindsay a,∗ , Robert Duncan Jr. a , S. Ansar Ahmed a , Anne M. Zajac a , J.P. Dubey b a Department of Biomedical Sciences and Pathobiology, Center for Molecular Medicine and Infectious Diseases, Virginia–Maryland Regional College of Veterinary Medicine, Virginia Tech., 1410 Prices Fork Road, Blacksburg, VA 24061-0342, USA b United States Department of Agriculture, Agricultural Research Service, Animal and Natural Resources Institute, Parasite Biology, Epidemiology and Systematics Laboratory, Beltsville, MD 20705-2350, USA Received 12 June 2001; received in revised form 21 August 2001; accepted 21 August 2001 Abstract Equine protozoal myeloencephalitis (EPM) is a neurologic syndrome in horses from the Americas and is usually caused by infection with the apicomplexan parasite, Sarcocystis neurona. Little is known about the role of immunobiological mediators to this parasite. Nitric oxide (NO) is important in resistance to many intracellular parasites. We, therefore, investigated the role of inducible and endothelial NO in resistance to clinical disease caused by S. neurona in mice. Groups of interferon- gene knockout (IFN--KO) mice, inducible nitric oxide synthase gene knockout (iNOS-KO) mice, endothelial nitric oxide synthase gene knockout (eNOS-KO) and appropriate genetic background mice (BALB/c or C57BL/6) were orally fed sporocysts or Hanks balanced salt solution. Mice were observed for signs of clinical disease and examined at necropsy. Clinical disease and deaths occurred only in the IFN--KO mice. Microscopic lesions were seen only in the brains of IFN--KO mice. Results of this study indicate that iNOS and eNOS are not major mediators of resistance to S. neurona infections. Results of this study suggest that IFN- mediated immunity to S. neurona may be mediated by non-NO-dependent mechanisms. © 2002 Elsevier Science B.V. All rights reserved. Keywords: Equine protozoal myeloencephalitis; Sarcocystis neurona; Nitric oxide; Interferon-; Knockout mice ∗ Corresponding author. Tel.: +1-540-231-6302; fax: +1-540-231-3426. E-mail address: lindsayd@vt.edu (D.S. Lindsay). 0304-4017/02/$ – see front matter © 2002 Elsevier Science B.V. All rights reserved. PII:S0304-4017(01)00555-6