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Department of

Pharmacology & Systems Physiology 

Photo of  A. John MacLennan, PhD

A. John MacLennan, PhD

Associate Professor

Education/Credentials
  • BSc: University of British Columbia
  • MA: University of Colorado
  • PhD: University of British Columbia
  • Postdoctoral Fellow: University of California, Los Angeles

Research/Clinical Interests

Our research focuses primarily on two critical, neuronal proteins (Ciliary Neurotrophic Factor Receptor ? [CNTFR?] and H218) and the roles they play in the development and maintenance of the nervous system. In order to directly study the functions these proteins serve in living mammals (mice), we use a wide variety of techniques including conditional and non-conditional genomic knockouts, viral-directed in vivo protein expression, computer-based microscopy and image analysis, stereotaxic surgery and slice electrophysiology. Evidence suggests that CNTFR? is required for the survival of developing neurons as well as the protection and natural repair of the nervous system following injury. A better understanding of how CNTFR? may perform these functions could lead to new treatments for neuronal injury and neurodegenerative diseases. H218 knockout mice develop epilepsy indicating that H218, a sphingosine 1-phosphate receptor, is essential for the development of proper neuronal excitability. Our H218 experiments are designed to exploit this novel model of epilepsy to determine how H218 regulates excitability. Such information may lead to H218-targeted therapeutics as well as the identification of human epilepsies involving H218 mutations.

Contact Information

Peer Reviewed Publications

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Lee, Nancy; Batt, Myra K; Cronier, Brigitte A; Jackson, Michele C; Bruno Garza, Jennifer L; Trinh, Dennis S; Mason, Carter O; Spearry, Rachel P; Bhattacharya, Shayon; Robitz, Rachel; Nakafuku, Masato; MacLennan, A John 2013. Ciliary neurotrophic factor receptor regulation of adult forebrain neurogenesis. The Journal of neuroscience : the official journal of the Society for Neuroscience, 33 3, 1241-58

Lee, Nancy; Rydyznski, Carolyn E; Spearry, Rachel P; Robitz, Rachel; Maclennan, A John 2013. The contribution of ciliary neurotrophic factor receptors to adult motor neuron survival in vivo is specific to insult type and distinct from that for embryonic motor neurons. The Journal of comparative neurology, 521 14, 3217-25

Lee, Nancy; Spearry, Rachel P; Leahy, Kendra M; Robitz, Rachel; Trinh, Dennis S; Mason, Carter O; Zurbrugg, Rebekah J; Batt, Myra K; Paul, Richard J; Maclennan, A John 2013. Muscle ciliary neurotrophic factor receptor ? promotes axonal regeneration and functional recovery following peripheral nerve lesion. The Journal of comparative neurology, 521 13, 2947-65

Stefater, M A; MacLennan, A J; Lee, N; Patterson, C M; Haller, A; Sorrell, J; Myers, M; Woods, S C; Seeley, R J 2012. The anorectic effect of CNTF does not require action in leptin-responsive neurons. Endocrinology, 153 6, 2647-54

Cattoretti, Giorgio; Mandelbaum, Jonathan; Lee, Nancy; Chaves, Alicia H; Mahler, Ashley M; Chadburn, Amy; Dalla-Favera, Riccardo; Pasqualucci, Laura; MacLennan, A John 2009. Targeted disruption of the S1P2 sphingosine 1-phosphate receptor gene leads to diffuse large B-cell lymphoma formation. Cancer research, 69 22, 8686-92

Lee, Nancy; Robitz, Rachel; Zurbrugg, Rebekah J; Karpman, Adam M; Mahler, Ashley M; Cronier, Samantha A; Vesey, Rachel; Spearry, Rachel P; Zolotukhin, Sergei; Maclennan, A John 2008. Conditional, genetic disruption of ciliary neurotrophic factor receptors reveals a role in adult motor neuron survival. The European journal of neuroscience, 27 11, 2830-7

Lorenz, John N; Arend, Lois J; Robitz, Rachel; Paul, Richard J; MacLennan, A John 2007. Vascular dysfunction in S1P2 sphingosine 1-phosphate receptor knockout mice. American journal of physiology. Regulatory, integrative and comparative physiology, 292 1, R440-6

Miotke, Jill A; MacLennan, A John; Meyer, Ronald L 2007. Immunohistochemical localization of CNTFRalpha in adult mouse retina and optic nerve following intraorbital nerve crush: evidence for the axonal loss of a trophic factor receptor after injury. The Journal of comparative neurology, 500 2, 384-400

MacLennan, A John; Benner, Shannon J; Andringa, Anastasia; Chaves, Alicia H; Rosing, Joanna L; Vesey, Rachel; Karpman, Adam M; Cronier, Samantha A; Lee, Nancy; Erway, Larry C; Miller, Marian L 2006. The S1P2 sphingosine 1-phosphate receptor is essential for auditory and vestibular function. Hearing research, 220 1-2, 38-48

Lee, Nancy; Neitzel, Karen L; Di Marco, Annalise; Laufer, Ralph; MacLennan, A John 2005. Penetrating brain injury leads to activation of ciliary neurotrophic factor receptors. Neuroscience letters, 374 3, 161-5

Lee, Nancy; Neitzel, Karen L; Devlin, Brenda K; MacLennan, A John 2004. STAT3 phosphorylation in injured axons before sensory and motor neuron nuclei: potential role for STAT3 as a retrograde signaling transcription factor. The Journal of comparative neurology, 474 4, 535-45

Aberg, M A; Ryttsén, F; Hellgren, G; Lindell, K; Rosengren, L E; MacLennan, A J; Carlsson, B; Orwar, O; Eriksson, P S 2001. Selective introduction of antisense oligonucleotides into single adult CNS progenitor cells using electroporation demonstrates the requirement of STAT3 activation for CNTF-induced gliogenesis. Molecular and cellular neurosciences, 17 3, 426-43

MacLennan, A J; Carney, P R; Zhu, W J; Chaves, A H; Garcia, J; Grimes, J R; Anderson, K J; Roper, S N; Lee, N 2001. An essential role for the H218/AGR16/Edg-5/LP(B2) sphingosine 1-phosphate receptor in neuronal excitability. The European journal of neuroscience, 14 2, 203-9

MacLennan, A J; Devlin, B K; Marks, L; Gaskin, A A; Neitzel, K L; Lee, N 2000. Antisense studies in PC12 cells suggest a role for H218, a sphingosine 1-phosphate receptor, in growth-factor-induced cell-cell interaction and neurite outgrowth. Developmental neuroscience, 22 4, 283-95

MacLennan, A J; Neitzel, K L; Devlin, B K; Garcia, J; Hauptman, G A; Gloaguen, I; Di Marco, A; Laufer, R; Lee, N 2000. In vivo localization and characterization of functional ciliary neurotrophic factor receptors which utilize JAK-STAT signaling. Neuroscience, 99 4, 761-72

Varela, C R; Bengston, L; Xu, J; MacLennan, A J; Forger, N G 2000. Additive effects of ciliary neurotrophic factor and testosterone on motoneuron survival; differential effects on motoneuron size and muscle morphology. Experimental neurology, 165 2, 384-93

MacLennan, A J; Devlin, B K; Neitzel, K L; McLaurin, D L; Anderson, K J; Lee, N 1999. Regulation of ciliary neurotrophic factor receptor alpha in sciatic motor neurons following axotomy. Neuroscience, 91 4, 1401-13

MacLennan, A J; Orringer, M B; Beer, D G 1999. Identification of intestinal-type Barrett's metaplasia by using the intestine-specific protein villin and esophageal brush cytology. Molecular carcinogenesis, 24 2, 137-43

Chalazonitis, A; Rothman, T P; Chen, J; Vinson, E N; MacLennan, A J; Gershon, M D 1998. Promotion of the development of enteric neurons and glia by neuropoietic cytokines: interactions with neurotrophin-3. Developmental biology, 198 2, 343-65

Forger, N G; Wagner, C K; Contois, M; Bengston, L; MacLennan, A J 1998. Ciliary neurotrophic factor receptor alpha in spinal motoneurons is regulated by gonadal hormones. The Journal of neuroscience : the official journal of the Society for Neuroscience, 18 21, 8720-9

Li, Y; MacLennan, A J; Rogers, M B 1998. A putative G-protein-coupled receptor, H218, is down-regulated during the retinoic acid-induced differentiation of F9 embryonal carcinoma cells. Experimental cell research, 239 2, 320-5

Kordower, J H; Yaping-Chu, ; Maclennan, A J 1997. Ciliary neurotrophic factor receptor alpha-immunoreactivity in the monkey central nervous system. The Journal of comparative neurology, 377 3, 365-80

Maclennan, A J; Marks, L; Gaskin, A A; Lee, N 1997. Embryonic expression pattern of H218, a G-protein coupled receptor homolog, suggests roles in early mammalian nervous system development. Neuroscience, 79 1, 217-24

MacLennan, A J; McLaurin, D L; Marks, L; Vinson, E N; Pfeifer, M; Szulc, S V; Heaton, M B; Lee, N 1997. Immunohistochemical localization of netrin-1 in the embryonic chick nervous system. The Journal of neuroscience : the official journal of the Society for Neuroscience, 17 14, 5466-79

MacLennan, A J; Gaskin, A A; Vinson, E N; Martinez, L C 1996. Ciliary neurotrophic factor receptor alpha mRNA in NB41A3 neuroblastoma cells: regulation by cAMP. European journal of pharmacology, 295 1, 103-8

MacLennan, A J; Vinson, E N; Marks, L; McLaurin, D L; Pfeifer, M; Lee, N 1996. Immunohistochemical localization of ciliary neurotrophic factor receptor alpha expression in the rat nervous system. The Journal of neuroscience : the official journal of the Society for Neuroscience, 16 2, 621-30

MacLennan, A J; Lee, N; Walker, D W 1995. Chronic ethanol administration decreases brain-derived neurotrophic factor gene expression in the rat hippocampus. Neuroscience letters, 197 2, 105-8

Lado, D C; Browe, C S; Gaskin, A A; Borden, J M; MacLennan, A J 1994. Cloning of the rat edg-1 immediate-early gene: expression pattern suggests diverse functions. Gene, 149 2, 331-6

MacLennan, A J; Browe, C S; Gaskin, A A; Lado, D C; Shaw, G 1994. Cloning and characterization of a putative G-protein coupled receptor potentially involved in development. Molecular and cellular neurosciences, 5 3, 201-9

MacLennan, A J; Gaskin, A A; Lado, D C 1994. CNTF receptor alpha mRNA expression in rodent cell lines and developing rat. Brain research. Molecular brain research, 25 3-4, 251-6

MacLennan, A J; Lee, N; Vincent, S R; Walker, D W 1994. D2 dopamine receptor mRNA distribution in cholinergic and somatostatinergic cells of the rat caudate-putamen and nucleus accumbens. Neuroscience letters, 180 2, 214-8

Maclennan, A J; Shaw, G 1993. A yeast SH2 domain. Trends in biochemical sciences, 18 12, 464-5

Tobin, A J; Brecha, N; Chiang, M Y; Endo, S; Erlander, M G; Feldblum, S; Houser, C R; Kaufman, D L; Khrestchatistky, M; MacLennan, A J 1992. Alternative forms of GAD and GABAA receptors. Advances in biochemical psychopharmacology, 47 , 55-66

Khrestchatisky, M; MacLennan, A J; Tillakaratne, N J; Chiang, M Y; Tobin, A J 1991. Sequence and regional distribution of the mRNA encoding the alpha 2 polypeptide of rat gamma-aminobutyric acidA receptors. Journal of neurochemistry, 56 5, 1717-22

MacLennan, A J; Brecha, N; Khrestchatisky, M; Sternini, C; Tillakaratne, N J; Chiang, M Y; Anderson, K; Lai, M; Tobin, A J 1991. Independent cellular and ontogenetic expression of mRNAs encoding three alpha polypeptides of the rat GABAA receptor. Neuroscience, 43 2-3, 369-80

Tobin, A J; Khrestchatisky, M; MacLennan, A J; Chiang, M Y; Tillakaratne, N J; Xu, W T; Jackson, M B; Brecha, N; Sternini, C; Olsen, R W 1991. Structural, developmental and functional heterogeneity of rat GABAA receptors. Advances in experimental medicine and biology, 287 , 365-74

MacLennan, A J; Pelleymounter, M A; Atmadja, S; Jakubovic, A; Maier, S F; Fibiger, H C 1989. D2 dopamine receptors in the rat prefrontal cortex: characterization and alteration by stress. Brain research, 477 1-2, 300-7

Radke, J M; MacLennan, A J; Beinfeld, M C; Bissette, G; Nemeroff, C B; Vincent, S R; Fibiger, H C 1989. Effects of short- and long-term haloperidol administration and withdrawal on regional brain cholecystokinin and neurotensin concentrations in the rat. Brain research, 480 1-2, 178-83

MacLennan, A J; Atmadja, S; Lee, N; Fibiger, H C 1988. Chronic haloperidol administration increases the density of D2 dopamine receptors in the medial prefrontal cortex of the rat. Psychopharmacology, 95 2, 255-7

Radke, J M; MacLennan, A J; Vincent, S R; Fibiger, H C 1988. Comparison between short- and long-term haloperidol administration on somatostatin and substance P concentrations in the rat brain. Brain research, 445 1, 55-60

MacLennan, A J; Drugan, R C; Maier, S F 1983. Long-term stress-induced analgesia blocked by scopolamine. Psychopharmacology, 80 3, 267-8

MacLennan, A J; Maier, S F 1983. Coping and the stress-induced potentiation of stimulant stereotypy in the rat. Science (New York, N.Y.), 219 4588, 1091-3

MacLennan, A J; Drugan, R C; Hyson, R L; Maier, S F; Madden, J; Barchas, J D 1982. Dissociation of long-term analgesia and the shuttle box escape deficit caused by inescapable shock. Journal of comparative and physiological psychology, 96 6, 904-12

MacLennan, A J; Drugan, R C; Hyson, R L; Maier, S F; Madden, J; Barchas, J D 1982. Corticosterone: a critical factor in an opioid form of stress-induced analgesia. Science (New York, N.Y.), 215 4539, 1530-2

Beninger, R J; MacLennan, A J; Pinel, J P 1980. The use of conditioned defensive burying to test the effects of pimozide on associative learning. Pharmacology, biochemistry, and behavior, 12 3, 445-8

Wilkie, D M; MacLennan, A J; Pinel, J P 1979. Rat defensive behavior: burying noxious food. Journal of the experimental analysis of behavior, 31 3, 299-306

. The three papers described in section 8 , ,

Muthuvel Arumugam, Richard Ahrens, Heather Osterfeld, Leah C. Kottyan, Xun Shang, A. John Maclennan, Nives Zimmermann, Yi Zheng PhD, Fred. D. Finkelman, Simon P. Hogan . Increased Susceptibility of 129SvEvBrd mice to IgE-Mast cell mediated anaphylaxis , ,