We study the participation of various genes in appetitive behaviors using a molecular and functional genetics approach. In particular we are studying the role of the dopamine D2 receptor and the proopiomelanocortin genes interrogating the effect of different mutations in mice and zebrafish.

Lab Members

Dr. Flavio de Souza
Investigator Adjunct CONICET

Dra. Daniela Paula Orquera
Postdoctoral Fellow CONICET

Lic. Rodrigo Casas Cordero
Doctoral Fellow CONICET

Lic. Eric Casey
Doctoral Fellow CONICET

Lic. Daniela Rojo
Doctoral Fellow CONICET

María Agustina Villa
Doctoral Fellow CONICET

M. Belén Tavella
Agency Fellow

Lic. Clara Hael
Doctoral Fellow CONICET

Carolina Alvarez
Assistant Technician CONICET


Inducible ablation of dopamine D2 receptors in adult mice impairs locomotion, motor skill learning and leads to severe parkinsonism
Bello EP, Casas-Cordero R, Galiñanes GL, Casey E, Belluscio MA, Rodríguez V, Noaín D, Murer MG, Rubinstein M. (2017)
Mol Psychiatry 22:595-604.

Basal Ganglia Cell Dysfunction Contributes to Physical Inactivity in Obesity
Friend DM, Devarakonda K, O’Neal TJ, Skirzewski M, Papazoglou I, Kaplan AR, Liow JS, Guo J, Rane SG, Rubinstein M, Alvarez VA, Hall KD, Kravitz AV (2017)
Cell Metab. 25:312-321.

Reprogramming the body weight set point by a reciprocal interaction of hypothalamic leptin sensitivity and Pomc gene expression reverts extreme obesity.
Chhabra KH, Adams JM, Jones GL, Yamashita M, Schlapschy M, Skerra A, Rubinstein M, Low MJ. (2016)
Mol Metab. 5869-81.

Essential function of the transcription factor Rax in the early patterning of the mammalian hypothalamus.
Orquera DP, Nasif S, Low MJ, Rubinstein M, de Souza FS. (2016)
Developmental Biol. 416:212-24.

Enhanced GABA Transmission Drives Bradykinesia Following Loss of Dopamine D2 Receptor Signaling.
Lemos JC, Friend DM, Kaplan AR, Shin JH, Rubinstein M, Kravitz AV, Alvarez VA. (2016)
Neuron 90:824-38.

Dopamine Regulation of Lateral Inhibition between Striatal Neurons Gates the Stimulant Actions of Cocaine.
Dobbs LK, Kaplan AR, Lemos JC, Matsui A, Rubinstein M, Alvarez VA. (2016)
Neuron 90:1100-13.

Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria.
Chhabra KH, Adams JM, Fagel B, Lam DD, Qi N, Rubinstein M, Low MJ. (2016)
Diabetes 65:660-72.

Islet 1 specifies the identity of hypothalamic melanocortin neurons and is critical for normal food intake and adiposity in adulthood.
Nasif S, de Souza FS, González LE, Yamashita M, Orquera DP, Low MJ, Rubinstein M. (2015)
Proc Natl Acad Sci U S A. 112:E1861-70.

Loss of feedback inhibition via D2 autoreceptors enhances acquisition of cocaine taking and reactivity to drug-paired cues.
Holroyd KB, Adrover MF, Fuino RL, Bock R, Kaplan AR, Gremel CM, Rubinstein M, Alvarez VA. (2015)
Neuropsychopharmacology 40:1495-509.

Partially Redundant Enhancers Cooperatively Maintain Mammalian Pomc Expression Above a Critical Functional Threshold.
Lam DD, de Souza FSJ, Nasif S, Yamashita M, López-Leal R, Otero-Corchon V, Meece K, Mercer AJ, Wardlaw SL, Rubinstein M*, Low MJ* (2015)
PloS Genetics 11(2):e1004935.
*: autores co-responsables

Selective disruption of dopamine D2 receptors in pituitary lactotropes increases body weight and adiposity in female mice
Perez Millan MI*, Luque GM*, Ramirez MC, Noain D, Ornstein AM, Rubinstein Marcelo*, Becu-Villalobos D* (2014).
Endocrinology 55:829-39.
*: igual contribución

Enhancer turnover and conserved regulatory function in vertebrate evolution.
Domené S, Bumaschny VF, de Souza FSJ, Franchini LF, Nasif S, Low MJ, Rubinstein M (2013)
Phil Trans B Royal Soc 368:AOP doi: 10.1098/rstb.2013.0027

Enhancer evolution and animal diversity.
Rubinstein M, deSouza FJ (2013)
Phil Trans B Royal Soc 368:AOP doi: 10.1098/rstb.2013.0017 (Review)

Exaptation of transposable elements into novel cis-regulatory elements: is the evidence always strong?
de Souza FSJ, Franchini LF, Rubinstein M (2013)
Mol Biol Evol 30:1239-51. (Review)

Central dopamine D2 receptors regulate growth hormone-dependent body growth and pheromone signaling to conspecific males
Noaín D, Pérez-Millán MI, Bello EP, Luque GM, Casas Cordero R, Gelman DM, Peper M, García Tornadu I, Low MJ, Becu-Villalobos D, Rubinstein M (2013).
J Neurosci 33:5834-42

Obesity-programmed mice are rescued by early genetic intervention
Bumaschny VF, Yamashita M, Casas-Cordero R, Otero-Corchon V, de Souza FJ, Rubinstein M*, Low MJ* (2012).
J Clin Invest 122:4203-12.
*: autores co-responsables

Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors
Bello EP, Mateo Y, Gelman DM, Noaín D, Shin JH, Low MJ, Alvarez VA, Lovinger DM, Rubinstein M (2011).
Nat Neurosci. 14:1033-8.

Convergent evolution of two mammalian neuronal enhancers by sequential exaptation of unrelated retroposons
Franchini LF, López-Leal R, Nasif S, Beati P, Gelman DM, Low MJ, de Souza FJS, Rubinstein M (2011).
P Natl Acad Sci USA 108:5270-5

Ancient Exaptation of a CORE-SINE Retroposon into a Highly Conserved Mammalian Neuronal Enhancer of the Proopiomelanocortin Gene
Santangelo AM, de Souza FJS, Franchini LF, Bumaschny VF, Low MJ, Rubinstein M (2007).
PLoS Genetics 3:1813-26.

Transcriptional Regulation of Pituitary POMC Is Conserved at the Vertebrate Extremes in Spite of Great Promoter Sequence Divergence
Bumaschny VF, de Souza FJ, López Leal R, Santagenlo A, Levi DH, Baetscher M, Low MJ, Rubinstein M (2007).
Mol Endocrinol 21:2738-49.

Identification of Brain Neurons Expressing the Dopamine D4 Receptor Gene using BAC Transgenic Mice.
Noaín D, Avale ME, Wedemeyer C, Peper M, Rubinstein M (2006)
Eur J Neurosci 24:2429-2438.

Subfunctionalization of Expression and Peptide Domains Following the Ancient Duplication of the Proopiomelanocortin Gene in Teleost Fishes
de Souza FS, Bumaschny VF, Low MJ, Rubinstein M. (2005).
Mol Biol Evol. 22:2417-2427.

Identification of Neuronal Enhancers of the Proopiomelanocortin Gene by Transgenic Mouse Analysis and Phylogenetic Footprinting
de Souza FJS,. Santangelo AM, Bumaschny VF, Avale ME, Smart JL, Low MJ, Rubinstein M (2005).
Mol Cell Biol 25:3076-86.

A Transgenic Marker for Newly Born Granule Cells in Dentate Gyrus.
Overstreet L, Hentges S, Bumaschny V, Souza FJ, Smart J, Santangelo A, Low M, Westbrook G, Rubinstein M (2004)
J Neurosci 23:3251-3259

The dopamine D4 receptor is essential for hyperactivity and impaired behavioral inhibition in a mouse model of attention deficit/hyperactivity disorder
Avale ME, Falzone TL, Gelman DM, Low MJ, Grandy DK, Rubinstein M (2004).
Mol Psychiatry 9:718-26.

Transgenic Mice Engineered to Target Cre/LoxP-Mediated DNA Recombination into Catecholaminergic Neurons.
Gelman DM, Noaín DC, Avale ME, Otero V,. Low MJ, Rubinstein M (2003)
Genesis 36:196-202.

A Role for the Endogenous Opioid beta-Endorphin in Energy Homeostasis
Appleyard SM, Hayward M, Young JI, Butler AA, Cone RD, Rubinstein M, Low MJ. (2003).
Endocrinology. 144:1753-1760

Activation of Central Melanocortin Pathways by Fenfluramine
Heisler LK, Cowley MA, Tecott LH, Fan W, Low MJ, Smart JL, Rubinstein M, Tatro J, Holstege H, Lee C, Cone R, Elmquist J (2002).
Science 297:609-611

Absence of dopamine D4 receptors results in enhanced reactivity to unconditioned, but not conditioned, fear.
Falzone TL, Gelman DG, Young JI, Grandy DK, Low MJ, Rubinstein M (2002)
Eur J Neurosci 15:158-64

Somatostatin is required for masculinization of growth hormone–regulated hepatic gene expression but not of somatic growth
Low MJ, Otero-Corchon V, Parlow AF, Ramirez JL, Kumar U, Patel YC Rubinstein M (2001).
J Clin Invest 107:1571-1580.

Dopamine D4 Receptor-Deficient Mice Display Cortical Hyperexcitability.
Rubinstein M, Cepeda C, Hurst RS, Altemus KL, Ariano MA, Falzone TL, Kozell LB, Meshul CK, Bunzow JR, LowMJ, Levine MS, Grandy DK (2001)
J Neurosci 21:3756-3763.

Leptin activates anorexigenic POMC neurons through a neural network in arcuate nucleus.
Cowley MA, Smart JL, Rubinstein M, Cerdán MG, Diano S, Horvath TL, Cone RD, Low MJ (2001)
Nature 411:480-484.

Alcohol preference and sensitivity are markedly reduced in mice lacking dopamine D2 receptors
Phillips TJ, Brown KJ, Burkhart-Kasch S, Wenger CD, Kelly MA, Rubinstein M, Grandy DK, Low MJ (1998).
Nature Neuroscience 1:610-615.

Authentic Cell-Specific and Developmentally Regulated Expression of Proopiomelanocortin Genomic Fragments in Hypothalamic and Hindbrain Neurons of Transgenic Mice
Young JI, Otero V, Cerdán MG, Falzone TL, Chan E-C, Low MJ, Rubinstein M (1998).
J Neurosci 18:6631-6640.

Locomotor activity in D2 dopamine receptor deficient mice is determined by gene dosage, genetic background and developmental adaptations.
Kelly MA, Rubinstein M, Phillips TJ, Lessov CN, Burkhart-Kasch S, Zhang G, Bunzow J, Fang Y, Gerhardt GA, Grandy DK, Low MJ (1998).
J Neurosci 18: 3010-3020.

Accurate Spatial and Temporal Transgene Expression Driven by a 3.8 Kilobase Promoter of the Bovine ß-casein Gene in the Lactating Mouse Mammary Gland.
Cerdán MG, Young JI, Zino E, Falzone TL, Otero V, Torres HN, Rubinstein M (1998)
Mol Reprod Dev 49:236-245.

Mice Lacking Dopamine D4 Receptors Are Supersensitive to Ethanol, Cocaine and Methamphetamine.
Rubinstein M, Phillips TJ, Bunzow JR, Falzone TL, Dziewczapolski G, Pugsley TA, Zhang G, Fang Y, Larson JL, McDougall JA, ChesterJA, Saez C, Gershanik O, Low MJ, Grandy DK (1997)
Cell 90:991-1001.

Pituitary lactotroph hyperplasia and chronic hyperprolactinemia in dopamine D2 receptor-deficient mice.
Kelly MA*, Rubinstein M*, Asa SL, Zhang G, Saez C, Bunzow JR, Allen RG, Hnasko R, Ben-Jonathan N, Grandy DK, Low MJ (1997)
Neuron 19:103-113.
*: Estos dos autores contribuyeron igualmente.

Absence of Opioid Stress-Induced Analgesia in Mice Lacking ß-Endorphin by Targeted Mutagenesis.
Rubinstein M, Mogil JS, Japón MA, Chan EC, Allen RG, Low MJ (1996)
Proc Natl Acad Sci USA 93:3995-4000.

In situ hybridizarion analysis of anterior pituitary hormone gene expression during fetal mouse development.
Japón MA, Rubinstein M, Low MJ (1994)
J Histochem Cytochem 42:1117-1125.

Rat and mouse proopiomelanocortin gene sequences target tissue-specific expression to the pituitary gland but not to the hypothalamus of transgenic mice.
Rubinstein M, Mortrud M, Liu B, Low MJ (1993)
Neuroendocrinol 58:373-380.

Introduction of a point mutation into the genome by homologous recombination in embryonic stem cells using a replacement type vector with a selectable marker.
Rubinstein M, Japón MA, Low MJ (1993)
Nucleic Acid Res 21:2613-2617.

Adaptative mechanisms of striatal D1 and D2 dopamine receptors in response to a prolonged reserpine treatment in mice.
Rubinstein M, Muschietti JP, Gershanik O, Flawiá MM, Stefano FJE 1990
J Pharmacol Exp Therap 252:810-816.

Different roles of D-1 and D-2 dopamine receptors involved in locomotor activity of supersensitive mice.
Rubinstein M, Gershanik O, Stefano FJE 1988
Europ J Pharmacol 148:419-426.

Ex Lab Members

Juan Isaac Young. Doctor en Ciencias Biológicas, FCEyN, UBA (1998)
Marcelo Guido Cerdán. Doctor en Ciencias Biológicas, FCEyN, UBA. (1999)
Natalia V. De Marco. Licenciada en Ciencias Biológicas, FCEyN, UBA.(1999)
Verónica Otero. Doctora en Ciencias Biológicas, FCEyN, UBA. (2000)
Sebastián Kraves. Licenciado en Ciencias Biológicas, FCEyN, UBA. (2000)
Tomás Falzone. Doctor en Ciencias Biológicas, FCEyN, UBA. (2002)
Diego Matías Gelman. Doctor en Ciencias Biológicas, FCEyN, UBA. (2003)
María Elena Avale. Doctora en Ciencias Biológicas, FCEyN, UBA (2004)
Andrea Mariana Santangelo. Doctora en Ciencias Biológicas, FCEyN, UBA. (2006)
Viviana Florencia Bumaschny. Doctora en Medicina. Facultad de Medicina, Universidad de Buenos Aires. (2006)
Sergio Iván Nemirovsky. Doctor en Ciencias Biológicas. FCEyN, UBA. (2008)
Hugo Roa-Rojas. Bioquímico de la Universidad Austral de Chile, Valdivia, Chile.(2008)
Daniela Clara Noaín. Doctora en Ciencias Biológicas. FCEyN, UBA. (2008)
Marcela Peper. Doctora en Ciencias Biológicas. FCEyN, UBA. (2009)
María Inés Pérez-Millán. Doctora en Ciencias Biológicas. FCEyN, UBA. (2010)
Hernán Pérez. Licenciado en Ciencias Biológicas. FCEyN, Universidad de Buenos Aires (2010)
Rodrigo López-Leal. Doctor en Ciencias Mención Biología, Universidad Austral de Chile. (2012)
Estefanía Pilar Bello. Doctora en Ciencias Biológicas. FCEyN, UBA. (2012)
Sofía Nasif. Doctora en Ciencias Biológicas. FCEyN, UBA (2014)
Juan Ramiro Lorenzo López. Doctor en Ciencias Biológicas. FCEyN, Universidad de Buenos Aires (2015)

  • Superior Investigator CONICET.
  • Associate Professor, DFBMC, FCEyN, UBA.
  • Acting Director, INGEBI.
  • Undergraduate degree in Chemistry, FCEyN, UBA. 1986.
  • Ph. D. in Chemistry, UBA. 1989.
  • Postdoctoral Fellow Vollum Institute, Oregon Health & Sciences University, EEUU. 1990 – 1993.
  • Member of the Career of the Investigator CONICET Argentina. 1993.
  • Adjunct Professor, FCEyN, UBA. 1994.
  • International Research Scholar Howard Hughes Medical Institute. 1997 – 2012.
  • Fellow of the John Simon Guggenheim Memorial Foundation. 2002.
  • Chairman of the Dept. Physiology, Molecular and Cellular Biology DFBMC, FCEyN, UBA. 2010 – 2012.
  • Superior Investigator, CONICET Argentina. 2012 – Cont.
  • Adjunct Professor , Dept. Molecular and Integrative Physiology, University of Michigan, EEUU. 2013 – Cont.
  • Prize in Biology. The World Academy of Sciences (TWAS). 2014.
  • Associate Professor , DFBMC, FCEyN, UBA. 2015.
  • Acting Director , INGEBI, CONICET Argentina. 2015 – Cont.
  • International Scientific Advisory Board of the International Clinical Research Center, St. Anne’s University Hospital Brno, Czech Republic. 2015 – Cont.
  • Elected member of The World Academy of Sciences (TWAS). 2016.
  • Elected member of the Academy of Sciences of Latin America (ACAL). 2017.