Gene expression profiling reveals an inflammatory process in the anx/anx mutant mice.

Anorexia (anx) is a recessive mutation that causes lethal starvation in homozygous mice. Studies of anx/anx mice hypothalamus have shown abnormalities in the orexigenic (NPY/AGRP neurons) and the anorexigenic (POMC/CART neurons) pathways. By gene expression profiling using cDNA and oligonucleotide microarrays, we have shown that a surexpression of genes involved in inflammatory process occurred in anx mice hypothalamus. This inflammatory process could be the cause of the anorexia phenotype observed in these mice.

[1]  Denis Vivien,et al.  Cytokines in neuroinflammation and Alzheimer's disease. , 2004, Current drug targets.

[2]  S. Dryden,et al.  The serotonergic agent fluoxetine reduces neuropeptide y levels and neuropeptide y secretion in the hypothalamus of lean and obese rats , 1996, Neuroscience.

[3]  D. Dormont,et al.  Gene Expression in Scrapie , 1998, The Journal of Biological Chemistry.

[4]  M. Dalakas,et al.  A Study of the Interferon Antiviral Mechanism: Apoptosis Activation by the 2–5A System , 1997, The Journal of experimental medicine.

[5]  L. Steinman,et al.  Transcriptional analysis of targets in multiple sclerosis , 2003, Nature Reviews Immunology.

[6]  Carrolee Barlow,et al.  Software and methods for oligonucleotide and cDNA array data analysis , 2002, Genome Biology.

[7]  R. Kurth,et al.  Identification of Upregulated Genes in Scrapie-Infected Brain Tissue , 2000, Journal of Virology.

[8]  S. Ludwin,et al.  Microarray analysis of gene expression in multiple sclerosis and EAE identifies 5-lipoxygenase as a component of inflammatory lesions , 2001, Journal of Neuroimmunology.

[9]  H. Chun,et al.  Identification of genes showing differential expression in anorexia mutant mouse , 2003, Neuroreport.

[10]  T. Hökfelt,et al.  Hypothalamic neurohistochemistry of the murine anorexia (anx/anx) mutation: Altered processing of neuropeptide Y in the arcuate nucleus , 1997, The Journal of comparative neurology.

[11]  T. Hökfelt,et al.  Hypothalamic and vagal neuropeptide circuitries regulating food intake , 2001, Physiology & Behavior.

[12]  Jorge R. Oksenberg,et al.  The Influence of the Proinflammatory Cytokine, Osteopontin, on Autoimmune Demyelinating Disease , 2001, Science.

[13]  T. Joh,et al.  Neuropeptide Y mRNA and serotonin innervation in the arcuate nucleus of anorexia mutant mice , 1998, Brain Research.

[14]  T. Hökfelt,et al.  Approaches to anorexia in rodents: focus on the anx/anx mouse. , 2003, European journal of pharmacology.

[15]  Chang-Ju Kim,et al.  Increases in cell proliferation and apoptosis in dentate gyrus of anorexia (anx/anx) mice , 2001, Neuroscience Letters.

[16]  A. Inui.  Cancer Anorexia‐Cachexia Syndrome: Current Issues in Research and Management , 2002, CA: a cancer journal for clinicians.

[17]  R. Silverman,et al.  Interferon action and apoptosis are defective in mice devoid of 2′,5′‐oligoadenylate‐dependent RNase L , 1997, The EMBO journal.

[18]  S. Crow,et al.  Cytokine production in patients with anorexia nervosa, bulimia nervosa, and obesity. , 2000, The International journal of eating disorders.

[19]  T. Hökfelt,et al.  Changes in Neuropeptide Y Receptors and Pro-Opiomelanocortin in the Anorexia (anx/anx) Mouse Hypothalamus , 1999, The Journal of Neuroscience.

[20]  T. Hökfelt,et al.  The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[21]  L. Maltais,et al.  Anorexia, a recessive mutation causing starvation in preweanling mice. , 1984, The Journal of heredity.

[22]  D. H. Park,et al.  Drastic and selective hyperinnervation of central serotonergic neurons in a lethal neurodevelopmental mouse mutant, Anorexia (anx). , 1994, Brain research. Molecular brain research.

[23]  Matthew A. Zapala,et al.  Elevated gene expression levels distinguish human from non-human primate brains , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[24]  T. Hökfelt,et al.  Hypothalamic CART and serum leptin levels are reduced in the anorectic (anx/anx) mouse. , 2000, Brain research. Molecular brain research.

[25]  Jorge R. Oksenberg,et al.  Gene-microarray analysis of multiple sclerosis lesions yields new targets validated in autoimmune encephalomyelitis , 2002, Nature Medicine.