scholarly journals Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice

Cell ◽  
1995 ◽  
Vol 83 (2) ◽  
pp. 269-278 ◽  
Author(s):  
Ludwig Aigner ◽  
Silvia Arber ◽  
Josef P. Kapfhammer ◽  
Thorsten Laux ◽  
Corinna Schneider ◽  
...  
1997 ◽  
Vol 136 (3) ◽  
pp. 679-692 ◽  
Author(s):  
Pico Caroni ◽  
Ludwig Aigner ◽  
Corinna Schneider

Long-term functional plasticity in the nervous system can involve structural changes in terminal arborization and synaptic connections. To determine whether the differential expression of intrinsic neuronal determinants affects structural plasticity, we produced and analyzed transgenic mice overexpressing the cytosolic proteins cortical cytoskeleton–associated protein 23 (CAP-23) and growth-associated protein 43 (GAP-43) in adult neurons. Like GAP-43, CAP-23 was downregulated in mouse motor nerves and neuromuscular junctions during the second postnatal week and reexpressed during regeneration. In transgenic mice, the expression of either protein in adult motoneurons induced spontaneous and greatly potentiated stimulus-induced nerve sprouting at the neuromuscular junction. This sprouting had transgene-specific features, with CAP-23 inducing longer, but less numerous sprouts than GAP-43. Crossing of the transgenic mice led to dramatic potentiation of the sprout-inducing activities of GAP-43 and CAP-23, indicating that these related proteins have complementary and synergistic activities. In addition to ultraterminal sprouting, substantial growth of synaptic structures was induced. Experiments with pre- and postsynaptic toxins revealed that in the presence of GAP-43 or CAP-23, sprouting was stimulated by a mechanism that responds to reduced transmitter release and may be independent of postsynaptic activation. These results demonstrate the importance of intrinsic determinants in structural plasticity and provide an experimental approach to study its role in nervous system function.


2008 ◽  
Vol 17 (6) ◽  
pp. 1103-1116 ◽  
Author(s):  
Samuel McLenachan ◽  
Yona Goldshmit ◽  
Kerry J. Fowler ◽  
Lucille Voullaire ◽  
Timothy P. Holloway ◽  
...  

2000 ◽  
Vol 95 (1-2) ◽  
pp. 23-34 ◽  
Author(s):  
Johannes Beckers ◽  
Alicia Caron ◽  
Martin Hrabé de Angelis ◽  
Stefan Hans ◽  
José A. Campos-Ortega ◽  
...  

2011 ◽  
Vol 20 (4) ◽  
pp. 181-188 ◽  
Author(s):  
He-Jin Lee ◽  
Ji-Eun Suk ◽  
Kyung-Won Lee ◽  
Seung-Hwa Park ◽  
Peter C. Blumbergs ◽  
...  

Cell ◽  
1994 ◽  
Vol 76 (1) ◽  
pp. 117-129 ◽  
Author(s):  
David Westaway ◽  
Stephen J. DeArmond ◽  
Juliana Cayetano-Canlas ◽  
Darlene Groth ◽  
Dallas Foster ◽  
...  

2006 ◽  
Vol 27 (3) ◽  
pp. 391-397 ◽  
Author(s):  
Yvonne N. Tallini ◽  
Bo Shui ◽  
Kai Su Greene ◽  
Ke-Yu Deng ◽  
Robert Doran ◽  
...  

The peripheral nervous system has complex and intricate ramifications throughout many target organ systems. To date this system has not been effectively labeled by genetic markers, due largely to inadequate transcriptional specification by minimum promoter constructs. Here we describe transgenic mice in which enhanced green fluorescent protein (eGFP) is expressed under the control of endogenous choline acetyltransferase (ChAT) transcriptional regulatory elements, by knock-in of eGFP within a bacterial artificial chromosome (BAC) spanning the ChAT locus and expression of this construct as a transgene. eGFP is expressed in ChATBAC-eGFP mice in central and peripheral cholinergic neurons, including cell bodies and processes of the somatic motor, somatic sensory, and parasympathetic nervous system in gastrointestinal, respiratory, urogenital, cardiovascular, and other peripheral organ systems. Individual epithelial cells and a subset of lymphocytes within the gastrointestinal and airway mucosa are also labeled, indicating genetic evidence of acetylcholine biosynthesis. Central and peripheral neurons were observed as early as 10.5 days postcoitus in the developing mouse embryo. ChATBAC-eGFP mice allow excellent visualization of all cholinergic elements of the peripheral nervous system, including the submucosal enteric plexus, preganglionic autonomic nerves, and skeletal, cardiac, and smooth muscle neuromuscular junctions. These mice should be useful for in vivo studies of cholinergic neurotransmission and neuromuscular coupling. Moreover, this genetic strategy allows the selective expression and conditional inactivation of genes of interest in cholinergic nerves of the central nervous system and peripheral nervous system.


2017 ◽  
Vol 76 (12) ◽  
pp. 1046-1057 ◽  
Author(s):  
Nicolas Naudet ◽  
Emilie Antier ◽  
Damien Gaillard ◽  
Eric Morignat ◽  
Latifa Lakhdar ◽  
...  

2002 ◽  
Vol 76 (23) ◽  
pp. 12223-12232 ◽  
Author(s):  
Susanna Freude ◽  
Jürgen Hausmann ◽  
Markus Hofer ◽  
Ngan Pham-Mitchell ◽  
Iain L. Campbell ◽  
...  

ABSTRACT Targeted expression of biologically active interleukin-12 (IL-12) in astrocytes of the central nervous system (CNS) results in spontaneous neuroimmunological disease of aged mice. Borna disease virus (BDV) can readily multiply in the mouse CNS but does not trigger disease in most strains. Here we show that a large percentage of IL-12 transgenic mice developed severe ataxia within 5 to 10 weeks after infection with BDV. By contrast, no disease developed in mock-infected IL-12 transgenic and wild-type mice until 4 months of age. Neurological symptoms were rare in infected wild-type animals, and if they occurred, these were milder and appeared later. Histological analyses showed that the cerebellum of infected IL-12 transgenic mice, which is the brain region with strongest transgene expression, contained large numbers of CD4+ and CD8+ T cells as well as lower numbers of B cells, whereas other parts of the CNS showed only mild infiltration by lymphocytes. The cerebellum of diseased mice further showed severe astrogliosis, calcifications and signs of neurodegeneration. BDV antigen and nucleic acids were present in lower amounts in the inflamed cerebellum of infected transgenic mice than in the noninflamed cerebellum of infected wild-type littermates, suggesting that IL-12 or IL-12-induced cytokines exhibited antiviral activity. We propose that BDV infection accelerates the frequency by which immune cells such as lymphocytes and NK cells enter the CNS and then respond to IL-12 present in the local milieu causing disease. Our results illustrate that infection of the CNS with a virus that is benign in certain hosts can be harmful in such normally disease-resistant hosts if the tissue is unfavorably preconditioned by proinflammatory cytokines.


Sign in / Sign up

Export Citation Format

Share Document