Skip to main content
SpringerLink
Log in

The Anorexia Mouse

  • Chapter
Animal Models — Disorders of Eating Behaviour and Body Composition

  • 163 Accesses

Abstract

The anorexia (anx) mutation is an autosomal recessive and lethal mutation located on mouse chromosome 2. It causes severe malnutrition in preweanling mice as well as some neurological disturbances. Histological analyses show no abnormalities in the gastrointestinal system and blood parameters are normal. However, there are several interesting alterations of the distribution of many appetite regulating peptides in the hypothalamus of mutant mice. Serum leptin levels are also altered in anx/anx mice. The anx mouse is a useful model of malnutrition and particularly for exploring the role of hypothalamic regulation of food intake.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Ahima RS, Prabakaran DJ, Flier S. Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding. J Clin Invest 1998; 101: 1020–1027.

    Article  PubMed  CAS  Google Scholar 

  • Allen YS, Adrian TE, Allen JM, Tatemoto K, Crow TJ, Bloom SR, Polak JM. Neuropeptide Y distribution in the rat brain. Science 1983; 221: 877–879.

    Article  PubMed  CAS  Google Scholar 

  • Ashley DVM, Coscina DV, Harvey Anderson G. Selective decrease in protein intake following brain serotonin depletion. Life Sci 1979; 24: 973–984.

    Article  PubMed  CAS  Google Scholar 

  • Bai FL, Yamano M, Shiotani Y, Emson PC, Smith AD, Powell JF, Tohyama M. An arcuato-paraventricular and —dorsomedial hypothalamic neuropeptide Y-containing system which lacks noradrenaline in the rat. Brain Res 1985; 331: 172–175.

    Article  PubMed  CAS  Google Scholar 

  • Bloch B, Bugnon C, Fellmann D, Lenys D. Immunocytochemical evidence that the same neurones in the human infundibular nucleus are stained with anti-endorphins and antisera of other related peptides. Neurosci Lett 1978; 10: 147–152.

    Article  PubMed  CAS  Google Scholar 

  • Bloom F, Battenberg E, Rossier J, Ling N, Guillemin R. Neurones containing beta-endorphin in rat brain exist separately from those containing enkephalin: Immunocytochemical studies. Proc Natl Acad Sci USA 1978; 75: 1591–1595.

    Article  PubMed  CAS  Google Scholar 

  • Brady LS, Smith MA, Gold PW, Herkenham M. Altered expression of hypothalamic neuropeptide mRNAs in food-restricted and food-deprived rats. Neuroendocrinology 1990; 52: 441–447.

    Article  PubMed  CAS  Google Scholar 

  • Broberger C, Johansen J, Schalling M, Hökfelt T. Hypothalamic neurohistochemistry of the murine anorexia (anx/anx) mutation: altered processing of neuropeptide Y in the arcuate nucleus J Comp Neurol 1997a; 387: 124–135.

    Article  PubMed  CAS  Google Scholar 

  • Broberger C, Landry M, Wong H, Walsh J, Hökfelt T. Subtypes Y1 and Y2 of the neuropeptide Y receptor are respectively expressed in proopiomelanocortin and neuropeptide Y-containing neurones of the rat hypothalamic arcuate nucleus. Neuroendocrinology 1997b; 66: 393–408.

    Article  PubMed  CAS  Google Scholar 

  • Broberger C, Johansen J, Johansson C, Schalling M, Hökfelt T. The neuropeptide Y/agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice. Proc Natl Acad Sci USA 1998a; 95: 15043–15048.

    Article  PubMed  CAS  Google Scholar 

  • Broberger C, De Lecea L, Sutcliffe J.G, Hökfelt T. Hypocretin/Orexin- and melanin-concentrating hormone-expressing cells form distinct populations in the rodent lateral hypothalamus: Relationship to the neuropeptide Y and agouti gene-related protein systems J Comp Neurol 1998b; 402: 460–474.

    Article  PubMed  CAS  Google Scholar 

  • Broberger C, Johansen J, Brismar H, Johansson C, Schalling M, Hökfelt T. Changes in neuropeptide Y receptors and pro-opiomelanocortin in the anorexia (anx/anx) mouse hypothalamus. J Neuro sci 1999; 19: 7130–7139.

    CAS  Google Scholar 

  • Campfield LA, Smith FJ, Guisez Y, Devos R, Burn P. Recombinant mouse OB protein: evidence for a peripheral signal linking adiposity and central neural networks. Science 1995; 269: 546–549.

    Article  PubMed  CAS  Google Scholar 

  • Chronwall BM, DiMaggio DA, Massari VJ, Pickel VM, Ruggiero DA, O’Donohue TL. The anatomy of neuropeptide Y-containing neurones in rat brain Neuroscience 1985; 15: 1159–1181.

    Article  PubMed  CAS  Google Scholar 

  • Clark JT, Kalra PS, Crowley WR, Kalra SP. Neuropeptide Y and human pancreatic polypeptide stimulate feeding behavior in rats. Endocrinology 1984; 115: 427–429.

    Article  PubMed  CAS  Google Scholar 

  • Csiffáry A, Görcs TJ, Palkovits M. Neuropeptide Y innervation of ACTH-immunoreactive neurones in the arcuate nucleus of rats: a correlated light and electron microscopic double immunolabeling study. Brain Res 1990; 506: 215–222.

    Article  PubMed  Google Scholar 

  • Devaskar SU, Ollesch C, Rajakumar RA, Rajakumar PA. Developmental changes in ob gene expression and circulating leptin peptide concentrations Biochem Biophys Res Com 1997; 238: 44–47.

    Article  PubMed  CAS  Google Scholar 

  • deQuidt ME, Emson PC. Distribution of neuropeptide Y-like immunoreactivity in the rat central nervous system. Immunohistochemical analysis. Neuroscience 1986; 118: 545–618.

    Article  Google Scholar 

  • Douglass J, McKinzie AA, Couceyro P. PCR differential display identifies a rat brain mRNA that is transcriptionally regulated by cocaine and amphetamine. J Neurosci 1995; 15: 2471–2481.

    PubMed  CAS  Google Scholar 

  • Elias CF, Lee C, Kelly J, Aschkenasi C, Ahima RS, Couceyro PR, Kuhar MJ, Saper CB, Elmquist JK. Leptin activates hypothalamic CART neurones projecting to the spinal cord. Neuron 1998; 21: 1375–85.

    Article  PubMed  CAS  Google Scholar 

  • Elmquist JK, Maratos-Flier E, Saper CB, Flier JS. Unraveling the CNS pathways underlying responses to leptin Nat Neurosci 1998a; 1: 445–450.

    Article  PubMed  CAS  Google Scholar 

  • Elmquist JK, Bjorbaek C, Ahirna RS, Flier JS, Saper CB. Distributions of leptin receptor mRNA isoforms in the rat brain J Comp Neurol 1998b; 395: 535–547.

    Article  PubMed  CAS  Google Scholar 

  • Elmquist JK, Elias CF, Saper CB. From lesions to leptin: Hypothalamic control of food intake and body weight Neuron 1999; 22: 221–232.

    Article  PubMed  CAS  Google Scholar 

  • Everitt BJ, Meister B, Hökfelt T, Melander T, Terenius L, Rökaeus A, Theodorsson-Norheim E, Dockray G, Edwardson J, Cuello C, Elde R, Goldstein M, Hemmings H, Ouimet C, Walaas I, Greengard P, Vale W, Weber E, Wu J-Y, Chang K-J. The hypothalamic arcuate nucleus-median eminence Complex: Immunohistochemistry of transmitters, peptides and DARPP-32 with special reference to coexistence in dopamine neurones. Brain Res Rev 1986; 11: 97–155.

    Article  CAS  Google Scholar 

  • Fan W, Boston BA, Kesterson RA, Hruby VJ, Cone RD. Role of melanocortinergic neurones in feeding and the agouti obesity syndrome. Nature 1997; 385: 165–168.

    Article  PubMed  CAS  Google Scholar 

  • Fuxe K, Tinner B, Caberlotto L, Bunnemann B, Agnati LF. NPY Y1 receptor like immunoreactivity exists in a subpopulation of β-endorphin immunoreactive nerve cells in the arcuate nucleus: a double immunolabelling analysis in the rat Neurosci Lett 1997; 225: 49–52.

    Article  PubMed  CAS  Google Scholar 

  • Gerald C, Walker MW, Criscione L, Gustafson EL, Batzl-Hartmann C, Smith KE, Vaysse P, Durkin MM, Laz TM, Linemeyer DL, Schaffhauser AO, Whitebread S, Hofbauer KG, Taber RI, Branchek TA, Weinshank RL, A receptor subtype involved in neuropeptide-y-induced food intake Nature 1996; 382: 168–171.

    Article  PubMed  CAS  Google Scholar 

  • Grill HJ, Ginsberg AB, Seeley RJ, Kaplan JM. Brainstem application of melanocortin receptor ligands produces long-lasting effects on feeding and bodyweight. J Neurosci 1998; 18: 10128–10135.

    PubMed  CAS  Google Scholar 

  • Hahn TM, Breininger JF, Baskin DG, Schwartz MW. Coexpression of Agrp and NPY in fasting-activated hypothalamic neurons. Nat Neurosci 1998; 1: 271–272.

    Article  PubMed  CAS  Google Scholar 

  • Halaas JL, Gajiwala KS, Maffel M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman JF. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995; 269: 543–546.

    Article  PubMed  CAS  Google Scholar 

  • Håkansson ML, Brown H, Ghilardi N, Skoda RC, Meister B. Leptin receptor immunoreactivity in chemically defined target neurones of the hypothalamus. J Neurosci 1998; 18: 559–572.

    PubMed  Google Scholar 

  • Jacobs BL. Serotonin and behavior: emphasis on motor control J Clin Psychiatry 1991; 52 Suppl. 12: 17–23.

    PubMed  Google Scholar 

  • Jacobs BL, Azmitia EC. Structure and function of the brain serotonin system. Physiol Rev 1992; 72: 165–229.

    PubMed  CAS  Google Scholar 

  • Jahng JW, Houpt TA, Kim S-J, Joh TH, Son J.H. Neuropeptide Y mRNA and serotonin innervation in the arcuate nucleus of anorexia mutant mice. Brain Res 1998; 790: 67–73.

    Article  PubMed  CAS  Google Scholar 

  • Johansen JE, Broberger C, Lavebratt C, Johansson C, Kuhar MJ, Hökfelt T, Schalling M. Hypothalamic CART and serum leptin levels are reduced in the anorectic (anx/anx) mouse. Mol Brain Res (In press).

    Google Scholar 

  • Koylu EO, Couceyro PR, Lambert PD, Ling ND, DeSouza EB, Kuhar M.J. Immunohistochemical localization of novel CART peptides in rat hypothalamus, pituitary and adrenal gland. JNeuroendocrinol 1997; 11: 823–833.

    Google Scholar 

  • Kristensen P, Judge MJ, Thim L, Ribel U, Christjansen KN, Wulff BS, Clausen JT, Jensen PB, Madsen OD, Vrang N, Larsen PJ, Hastrup S. Hypothalamic CART is a new anorectic peptide regulated by leptin. Nature 1998; 393: 72–76.

    Article  PubMed  CAS  Google Scholar 

  • Lambert PD, Couceyro PR, McGirr KM, Dall Vechia SE, Smith Y, Kuhar M.J. CART peptides in the central control of feeding and interactions with neuropeptide Y. Synapse 1998; 29: 293–298.

    Article  CAS  Google Scholar 

  • Maltais LJ, Lane PW, Beamer WG. Anorexia, a recessive mutation causing starvation in preweanling mice. JHered 1984; 75: 468–472.

    CAS  Google Scholar 

  • Noach EL. Appetite regulation by serotoninergic mechanisms and effects of d-fenfluramine. Netherlands JMed 1994; 45: 123–133.

    CAS  Google Scholar 

  • Ollmann MM, Wilson BD, Yang Y-K, Kerns JA, Chen Y, Gantz I, Barsh GS. Antagonism of central. melanocortin receptors in vitro and in vivo by agouti-related protein. Science 1997; 278: 135–138.

    Article  PubMed  CAS  Google Scholar 

  • Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995; 269: 540–543.

    Article  PubMed  CAS  Google Scholar 

  • Pollock JD, Rowland N.E. Peripherally administered serotonin decreases food intake in rats. Pharmacol Biochem Behav 1981; 15: 179–183.

    Article  PubMed  CAS  Google Scholar 

  • Schwartz MW, Baskin DG, Bukowski TR, Kuijper JL, Foster D, Lasser G, Prunkard DE, Porte Jr D, Woods SC, Seeley RJ, Weigle DS. Specificity of leptin action on elevated blood glucose levels and hypothalamic neuropeptide Y gene expression in ob/ob mice. Diabetes 1996; 45: 531–535.

    Article  PubMed  CAS  Google Scholar 

  • Schwartz MW, Seeley RJ, Woods SC, Weigle DS, Campfield LA, Burn P, Baskin DG. Leptin increases hypothalamic pro-opiomelanocortin mRNA expression in the rostral arcuate nucleus. Diabetes 1997; 46: 2119–2123.

    Article  PubMed  CAS  Google Scholar 

  • Shor-Posner G, Grinker JA, Marinescu C, Brown O, Leibowitz SF. Hypothalamic serotonin in the control of meal patterns and macronutrient selection. Brain Res Bull 1986; 17: 663–671.

    Article  PubMed  CAS  Google Scholar 

  • Shutter JR, Graham M, Kinsey AC, Scully S, Lüthy R, Stark KL. Hypothalamic expression of ART, a novel gene related to agouti, is up-regulated in obese and diabetic mutant mice. Genes Dev 1997; 11: 593–602.

    Article  PubMed  CAS  Google Scholar 

  • Son JH, Baker H, Park DH, Joh T.H. Drastic and selective hyperinnervation of central serotonergic neurones in a lethal neurodevelopmental mouse mutant, Anorexia (anx). Mol Brain Res 1994; 25: 129–134.

    Article  PubMed  CAS  Google Scholar 

  • Stanley BG, Leibowitz SF. Neuropeptide Y injected in the paraventricular hypothalamus: A powerful stimulant of feeding behavior. Proc Natl Acad Sci USA 1985; 82: 3940–3943.

    Article  PubMed  CAS  Google Scholar 

  • Stanley BG, Magdalin W, Seirafi A, Nguyen MM, Leibowitz SF. Evidence for neuropeptide Y mediation of eating produced by food deprivation and for a variant of the Yl receptor mediating this peptide’s effect. Peptides 1992; 13: 581–587.

    Article  PubMed  CAS  Google Scholar 

  • Stephens TW, Basinski M, Bristow PK, Bue-Valleskey JM, Burgett SG, Craft L, Hale J, Hoffmann J, Hsiung HM, Kriauciunas A, MacKellar W, Rosteck Jr PR, Schoner B, Smith D, Tinsley FC, Zhang X-Y, Heiman M. The role of neuropeptide Y in the antiobesity action of the obese gene product. Nature 1995; 377: 530–532.

    Article  PubMed  CAS  Google Scholar 

  • Watson SJ, Akil H, Richard CW, Barchas JD. Evidence for two separate opiate peptide neuronal systems and the coexistence of beta-lipotropin, beta-endophin and ACTH imrnunoreactivities in the same hypothalamic neurones. Nature 1978; 275: 226–228.

    Article  PubMed  CAS  Google Scholar 

  • Woods AJ, Stock MJ. Leptin activation in hypothalamus. Nature 1996; 381: 745.

    Article  PubMed  CAS  Google Scholar 

  • Zhang X, Bao L, Xu Z-Q, Kopp J, Arvidsson U, Elde R, Hökfelt T. Localization of neuropeptide YY1 receptors in the rat nervous system with special reference to somatic receptors on small dorsal root ganglion neurones. Proc Natl Acad Sci USA 1994a; 91: 11738–11742.

    Article  PubMed  CAS  Google Scholar 

  • Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman J. Positional cloning ot the mouse obese gene and its human homologue. Nature 1994b; 372: 425–432.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Molecular Medicine, Neurogenetics Unit, Karolinska Institutet, Sweden

    Jeanette E. Johansen & Martin Schalling

Authors
  1. Jeanette E. Johansen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin Schalling
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of Wales, Bangor, UK

    John B. Owen

  2. Institute of Psychiatry, University of London, UK

    Janet L. Treasure  & David A. Collier  & 

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Johansen, J.E., Schalling, M. (2001). The Anorexia Mouse. In: Owen, J.B., Treasure, J.L., Collier, D.A. (eds) Animal Models — Disorders of Eating Behaviour and Body Composition. Springer, Dordrecht. https://doi.org/10.1007/978-94-015-9662-6_11

Download citation

  • DOI: https://doi.org/10.1007/978-94-015-9662-6_11

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-90-481-5743-3

  • Online ISBN: 978-94-015-9662-6

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation