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World J Gastroenterol. Mar 21, 2012; 18(11): 1141-1153
Published online Mar 21, 2012. doi: 10.3748/wjg.v18.i11.1141
Genetically modified mouse models for the study of nonalcoholic fatty liver disease
Perumal Nagarajan, M Jerald Mahesh Kumar, Ramasamy Venkatesan, Subeer S Majundar, Ramesh C Juyal
Perumal Nagarajan, Subeer S Majundar, Ramesh C Juyal, Small Animal Facility, National Institute of Immunology, New Delhi 110067, India
M Jerald Mahesh Kumar, Animal House, Centre for Cellular and Molecular Biology, Hyderabad 500007, India
Ramasamy Venkatesan, Animal House, JNU, New Delhi 110067, India
Author contributions: Nagarajan P drafted and wrote the article; Mahesh Kumar MJ and Venkatesan R collected literature and references; Nagarajan P, Majumdar SS and Juyal RC revised the manuscript critically.
Correspondence to: Dr. Perumal Nagarajan, Small Animal Facility, National Institute of Immunology, New Delhi 110067, India. naga73@yahoo.com
Telephone: +91-11-26703709 Fax: +91-11-26742125
Received: July 6, 2011
Revised: September 19, 2011
Accepted: October 28, 2011
Published online: March 21, 2012

Nonalcoholic fatty liver disease (NAFLD) is associated with obesity, insulin resistance, and type 2 diabetes. NAFLD represents a large spectrum of diseases ranging from (1) fatty liver (hepatic steatosis); (2) steatosis with inflammation and necrosis; to (3) cirrhosis. The animal models to study NAFLD/nonalcoholic steatohepatitis (NASH) are extremely useful, as there are still many events to be elucidated in the pathology of NASH. The study of the established animal models has provided many clues in the pathogenesis of steatosis and steatohepatitis, but these remain incompletely understood. The different mouse models can be classified in two large groups. The first one includes genetically modified (transgenic or knockout) mice that spontaneously develop liver disease, and the second one includes mice that acquire the disease after dietary or pharmacological manipulation. Although the molecular mechanism leading to the development of hepatic steatosis in the pathogenesis of NAFLD is complex, genetically modified animal models may be a key for the treatment of NAFLD. Ideal animal models for NASH should closely resemble the pathological characteristics observed in humans. To date, no single animal model has encompassed the full spectrum of human disease progression, but they can imitate particular characteristics of human disease. Therefore, it is important that the researchers choose the appropriate animal model. This review discusses various genetically modified animal models developed and used in research on NAFLD.

Keywords: Nonalcoholic fatty liver disease, Steatosis, Steatohepatitis, Knockout, Animal models