Analysis of Cutaneous Sensory Neurons in Transgenic Mice Lacking the Low Affinity Neurotrophin Receptor p75

Mice with a targeted mutation of the p75 low affinity neurotrophin receptor display smaller peripheral nerves and dorsal root ganglia. Here we show that transgenic mice have a significant elevation of thresholds to noxious mechanical and heat stimuli compared with p75+/+ control mice. Immunocytochemical analysis using antibodies against PGP 9.5 (a panaxonal marker) and calcitonin gene related peptide (CGRP, which labels peptidergic neurons) showed a reduction to 73% and 54%, respectively, of the epidermal innervation density. However, analysis of the cell size distribution of toluidine blue‐stained dorsal root ganglia showed no selective loss of neurons of particular diameters. Moreover, the neurochemical profile of dorsal root ganglia cells as defined by trkA, CGRP, I84 and RT97 immunostaining revealed no significant differences in comparison with p75+/+ animals. Staining of the dorsal horn of the spinal cord for CGRP and 164 was also normal in p75‐/‐animals. Taking into account a previously reported loss of ‐50% dorsal root ganglion neurons, we conclude that all types of sensory neurons are equally depleted in p75‐/‐ mice and that the absence of p75 impedes the development of more than one neuronal subtype.

[1]  S. Furukawa,et al.  [Neurotrophins and their receptors]. , 1997, Tanpakushitsu kakusan koso. Protein, nucleic acid, enzyme.

[2]  S. McMahon,et al.  Postnatal Changes in the Expression of the trkA High‐affinity NGF Receptor in Primary Sensory Neurons , 1996, The European journal of neuroscience.

[3]  R. Gerlai Gene-targeting studies of mammalian behavior: is it the mutation or the background genotype? , 1996, Trends in Neurosciences.

[4]  M. Bothwell p75NTR: A Receptor After All , 1996, Science.

[5]  Airaksinen,et al.  Analysis of cutaneous afferents in mice carrying targeted mutations of the BDNF gene , 1996 .

[6]  H. Thoenen,et al.  Specific Subtypes of Cutaneous Mechanoreceptors Require Neurotrophin-3 Following Peripheral Target Innervation , 1996, Neuron.

[7]  A. Davies,et al.  Developmental changes in NT3 signalling via TrkA and TrkB in embryonic neurons. , 1995, The EMBO journal.

[8]  S. McMahon,et al.  Immunocytochemical Localization of trkA Receptors in Chemically Identified Subgroups of Adult Rat Sensory Neurons , 1995, The European journal of neuroscience.

[9]  R. Jaenisch,et al.  Differential role of the low affinity neurotrophin receptor (p75) in retrograde axonal transport of the neurotrophins , 1995, Neuron.

[10]  Rudolf Jaenisch,et al.  Sensory but not motor neuron deficits in mice lacking NT4 and BDNF , 1995, Nature.

[11]  R. Vejsada,et al.  Neuronal deficits, not involving motor neurons, in mice lacking BDNF and/or NT4 , 1995, Nature.

[12]  W. Snider,et al.  Neurotrophin receptor mRNA expression defines distinct populations of neurons in rat dorsal root ganglia , 1995, The Journal of comparative neurology.

[13]  L. Mendell,et al.  Peripheral and Central Mechanisms of NGF‐induced Hyperalgesia , 1994, The European journal of neuroscience.

[14]  M. Barbacid The Trk family of neurotrophin receptors. , 1994, Journal of neurobiology.

[15]  G. Barrett,et al.  The p75 nerve growth factor receptor mediates survival or death depending on the stage of sensory neuron development. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[16]  G. Yancopoulos,et al.  The low affinity NGF receptor, p75, can collaborate with each of the Trks to potentiate functional responses to the neurotrophins , 1994, Neuron.

[17]  I. Fariñas,et al.  Severe sensory and sympathetic deficits in mice lacking neurotrophin-3 , 1994, Nature.

[18]  W. Snider,et al.  Functions of the neurotrophins during nervous system development: What the knockouts are teaching us , 1994, Cell.

[19]  Y. Barde,et al.  Sensory ganglia require neurotrophin-3 early in development. , 1994, Development.

[20]  R. Jaenisch,et al.  Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents , 1994, Cell.

[21]  G. Weskamp,et al.  TrkA cross-linking mimics neuronal responses to nerve growth factor. , 1994, Molecular biology of the cell.

[22]  D. Anderson,et al.  Expression of trk in MAH cells lacking the p75 low-affinity nerve growth factor receptor is sufficient to permit nerve growth factor-induced differentiation to postmitotic neurons. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[23]  R. Jaenisch,et al.  p75-deficient embryonic dorsal root sensory and neonatal sympathetic neurons display a decreased sensitivity to NGF. , 1994, Development.

[24]  G. Weskamp,et al.  Nerve growth factor and its low-affinity receptor promote Schwann cell migration. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[25]  S. McMahon,et al.  Mice lacking nerve growth factor display perinatal loss of sensory and sympathetic neurons yet develop basal forebrain cholinergic neurons , 1994, Cell.

[26]  I. Fariñas,et al.  Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development , 1994, Cell.

[27]  M. Barbacid,et al.  Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene , 1994, Nature.

[28]  R. Jaenisch,et al.  Dependence on p75 for innervation of some sympathetic targets. , 1994, Science.

[29]  Rudolf Jaenisch,et al.  Mice lacking brain-derived neurotrophic factor develop with sensory deficits , 1994, Nature.

[30]  A. Davies Neurotrophic Factors: Switching neurotrophin dependence , 1994, Current Biology.

[31]  M. Barbacid,et al.  Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death , 1993, Cell.

[32]  R. Jaenisch,et al.  p75-Deficient trigeminal sensory neurons have an altered response to NGF but not to other neurotrophins , 1993, Neuron.

[33]  L. Mendell,et al.  Nerve growth factor and nociception , 1993, Trends in Neurosciences.

[34]  G. Yancopoulos,et al.  The neurotrophins and their receptors. , 1993, Trends in cell biology.

[35]  M. Chao Neurotrophin receptors: A window into neuronal differentiation , 1992, Neuron.

[36]  E. Shooter,et al.  The nerve growth factor family of receptors , 1992, Trends in Neurosciences.

[37]  R. Jaenisch,et al.  Targeted mutation of the gene encoding the low affinity NGF receptor p75 leads to deficits in the peripheral sensory nervous system , 1992, Cell.

[38]  M. Barbacid,et al.  The trkB tyrosine protein kinase is a receptor for neurotrophin-4 , 1992, Neuron.

[39]  L. Kruger,et al.  Selective neuronal glycoconjugate expression in sensory and autonomic ganglia: relation of lectin reactivity to peptide and enzyme markers , 1990, Journal of neurocytology.

[40]  Y. Barde,et al.  Identification and characterization of a novel member of the nerve growth factor/brain-derived neurotrophic factor family , 1990, Nature.

[41]  P. Holzer,et al.  Local effector functions of capsaicin-sensitive sensory nerve endings: Involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides , 1988, Neuroscience.

[42]  R. Dubner,et al.  A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia , 1987, Pain.

[43]  D. Rohrlich,et al.  Counting sectioned cells via mathematical reconstruction , 1987, The Journal of comparative neurology.

[44]  E. Shooter,et al.  Gene transfer and molecular cloning of the rat nerve growth factor receptor , 1987, Nature.

[45]  M. Schwab,et al.  Brain-derived neurotrophic factor supports the survival of cultured rat retinal ganglion cells , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  A. Ross,et al.  Gene transfer and molecular cloning of the human NGF receptor. , 1986, Science.

[47]  A. Davies,et al.  The cranial sensory ganglia in culture: Differences in the response of placode-derived and neural crest-derived neurons to nerve growth factor☆ , 1985 .

[48]  C. Dalsgaard,et al.  Stimulation of connective tissue cell growth by substance P and substance K , 1985, Nature.

[49]  R. Levi‐montalcini,et al.  Nerve growth factor. , 1975, Science.

[50]  Fred E. D'Amour,et al.  A METHOD FOR DETERMINING LOSS OF PAIN SENSATION , 1941 .

[51]  M. Koltzenburg,et al.  The neurotrophin receptor p75 is involved in the regulation of bradykinin binding sites in cultured mouse sensory neurons , 1996 .

[52]  Y. Barde,et al.  Physiology of the neurotrophins. , 1996, Annual review of neuroscience.

[53]  H. Thoenen,et al.  Electrophysiological analysis of cutaneous sensory neurons in neonatal wildtype mice and transgenic animals lacking BDNF , 1995 .