Transgenic Animal Models for Brain 5-HT Deficiency: An Editorial Summary
Department of Neuroscience and Department of Neurology, School of Medicine and Public Health, Waisman Center, University of Wisconsin, Madison, WI 53705, USA
- *Corresponding Author:
- Jianfeng Lu
Department of Neuroscience and Department of Neurology
School of Medicine and Public Health, Waisman Center
University of Wisconsin, Madison, WI 53705, USA
E-mail: [email protected]
Received date: January 02, 2013; Accepted date:January 05, 2013; Published date: January 07, 2013
Citation: Lu J (2013) Transgenic Animal Models for Brain 5-HT Deficiency: An Editorial Summary. J Genet Syndr Gene Ther 4:e121. doi:10.4172/2157-7412.1000e121
Copyright: © 2013 Lu J. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and
source are credited.
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Animal: Pet-1 KO mice
First Report Year: 2003
Methods: Pet-1 Knock out
Lab: Evan Deneris
Loss of 5-HT Neurons: 80% deficiency of the central 5-HT neurons
Life Span and Body Weight: Survive to adult and normal body weight
• Heightened anxiety-like and aggressive behavior in adults .
• Extended and exacerbated period of breathing instability that occurs immediately after birth during which respiratory homeostasis is vulnerable to environmental challenges .
• Abnormal maternal behavior which affects offspring survival .
• A lack of cognitive deficits and an anxiety phenotype complicated by hypoactivity and defensiveness .
• Autoresuscitation responses to hypoxia-induced apnea are delayed in newborn mice .
• Altered ventilatory and thermoregulatory control .
• Bradycardia (the first 2 postnatal weeks) .
• Failed heart rate recovery at early age exposed to episodic anoxia .
• Autonomic dysregulation during mild cold stress in the neonatal period .
Animal: Lmx1b conditional KO mice
First Report Year: 2006
Methods: Conditional Lmx1b Knock out in pet1-expressing 5-HT neurons.
Labs: Zhou-Feng Chen, Yu-Qiang Ding and Lin Xu.
Loss of 5-HT Neurons: The initial generation of central 5-HT neurons appeared normal (at E11). However, the expression of both 5-HTspecific and non-5-HT-specific markers was lost in these neurons at later stages of development. Almost all central 5-HT neurons failed to survive.
Life Span and Body Weight: Survive to adult; and neonatal: lag in weight gain (because of hypoxia); adulthood: normal body weight.
• Normal locomotor activity .
• Neonatal: Frequent and severe apnea and high mortality .
• Adulthood: A blunted hypercapnic ventilatory response and impaired cold-induced thermogenesis (impaired shivering and brown adipose tissue activation) [12,13].
• Less sensitive to mechanical stimuli and exhibited enhanced inflammatory pain, the analgesic effect of several antidepressant drugs, including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants, was either abolished or greatly attenuated .
• Increase in wakefulness .
• Enhanced contextual fear memory .
Animal: Tph2 KO mice
First Report Year: 2008 
Methods: Tph2 Knock out
Labs: Katerina Savelieva, Klaus-Peter Lesch, Michael Bader, Gerard Karsenty, Donald M. Kuhn and Yi Rao.
Loss of 5-HT Neurons: Normal central 5-HT neuron formation.
Life Span and Body Weight: Survive to adult, growth retardation [18,19] and persistent leanness .
• More extended daytime sleep, suppressed respiration, altered body temperature control, and decreased blood pressure (BP) and heart rate (HR) during nighttime; Tph2 ko females, exhibit impaired maternal care leading to poor survival of their pups .
• Exaggerated aggression and decreased anxiety .
• A severe low bone mass phenotype affecting axial (vertebrae) and appendicular (long bones) skeleton while bone length and width were unaffected .
• Respond to METH in the same manner as wild-type controls, despite showing enhanced drug-induced hyperthermia .
• Substantial deficits in numerous validated tests of social interaction and communication; highly repetitive and compulsive behaviors; Newborn mice show delays in the expression of key developmental milestones and their diminished preference for maternal scents over the scent of an unrelated female is a forerunner of more severe socialization deficits that emerge in weanlings and persist into adulthood .
• Males did not show a preference between male and female bedding and genital odour .
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