Overexpression of growth-associated proteins in the neurons of adult transgenic mice

The Thy-1.2 expression cassette described in this report drives strong constitutive expression of transgenes specifically in the neurons of adult transgenic mice. Transgene expression begins at P6-10, at a time when it can affect activity-dependent rearrangements of synaptic connections and neuron-glia interactions during the late phases of nervous system development. Slightly earlier expression is detected in the developing cerebellum, where transgenes could also affect granule cell migration. Probably due to the strong genetic context sensitivity of the expression construct, expression patterns differ considerably among transgenic lines. Accordingly, neuron types can be subdivided into a group that consistently displays substantial expression in all tested transgenic lines, and in those where expression is founder-specific. About a fifth of the transgenic lines displayed quite generalized expression in neurons. These properties of the Thy-1.2 expression cassette can be exploited to study the effects of transgenes during late nervous system development and in the adult, with the added opportunity of analyzing different combinations of expressing and non-expressing neurons in transgenic animals derived from different founder lines.

[1]  N. Perrone-Bizzozero,et al.  Posttranscriptional regulation of GAP-43 gene expression in PC12 cells through protein kinase C-dependent stabilization of the mRNA , 1993, The Journal of cell biology.

[2]  M. Gossen,et al.  Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[3]  M. Vidal,et al.  Olfactory marker protein gene: its structure and olfactory neuron-specific expression in transgenic mice. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[4]  P. Caroni,et al.  The downregulation of growth-associated proteins in motoneurons at the onset of synapse elimination is controlled by muscle activity and IGF1 , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  M. Vidal,et al.  Tissue‐specific control elements of the Thy‐1 gene. , 1990, The EMBO journal.

[6]  W. Thompson,et al.  Nerve sprouting in muscle is induced and guided by processes extended by schwann cells , 1995, Neuron.

[7]  J. Silver,et al.  Regulation of Thy-1 gene expression in transgenic mice , 1987, Cell.

[8]  A. Routtenberg,et al.  A membrane phosphoprotein associated with neural development, axonal regeneration, phospholipid metabolism, and synaptic plasticity , 1987, Trends in Neurosciences.

[9]  H. Orr,et al.  Purkinje cell protein-2 regulatory regions and transgene expression in cerebellar compartments. , 1991, Genes & development.

[10]  J. Skene.  Axonal growth-associated proteins. , 1989, Annual review of neuroscience.

[11]  S. Hattori,et al.  Purification and molecular cloning of a novel acidic calmodulin binding protein from rat brain. , 1993, The Journal of biological chemistry.

[12]  D. Storm,et al.  Regulation of free calmodulin levels by neuromodulin: neuron growth and regeneration. , 1990, Trends in pharmacological sciences.

[13]  R. Morris.  Thy-1, the enigmatic extrovert on the neuronal surface. , 1992, BioEssays : news and reviews in molecular, cellular and developmental biology.

[14]  M. C. Brown.  Sprouting of motor nerves in adult muscles: a recapitulation of ontogeny , 1984, Trends in Neurosciences.

[15]  T. Getchell,et al.  Human and rodent OMP genes: conservation of structural and regulatory motifs and cellular localization. , 1994, Genomics.

[16]  J. Kapfhammer,et al.  Overexpression of the neural growth-associated protein GAP-43 induces nerve sprouting in the adult nervous system of transgenic mice , 1995, Cell.

[17]  P. Caroni,et al.  Identification, localization, and primary structure of CAP-23, a particle-bound cytosolic protein of early development , 1990, The Journal of cell biology.