Expression of a human insulin transgene in cholinergic neurons of the mouse medial habenula

Douhet, Philippe; Destrade, Claude; Bucchini, Danielle; Calas, A.

doi:10.1016/0248-4900(96)85274-9

Cited by 4 publications

(2 citation statements)

References 30 publications

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“…In these mice, LacZ reporter gene activity was restricted exclusively to the MH. Intriguingly, transgenic mice harbouring a 168-bp fragment of the human insulin gene promoter (as well as 5.5 kb of intronic sequence) fused to the LacZ reporter gene, also displayed an essentially identical expression pro®le (Douhet et al, 1995). We reasoned that a habenula-speci®c DNA element that directs expression to this compartment might be present in both the insulin and t-PA promoters.…”

Section: Lipopolysaccharide (Lps) Treatment Induces Lacz Expression Imentioning

confidence: 99%

Control elements between −9.5 and −3.0 kb in the human tissue‐type plasminogen activator gene promoter direct spatial and inducible expression to the murine brain

Schleuning²,

Michl³

et al. 2001

Eur J of Neuroscience

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Tissue-type plasminogen activator (t-PA) participates in the control of synaptic plasticity and memory formation in the central nervous system (CNS). Transgenic mice harbouring either 9.5, 3.0 or 1.4 kb of the human t-PA promoter fused to the LacZ reporter gene were used to assess t-PA promoter-directed expression in vivo. The 9.5 kb t-PA promoter directed expression to the brain, most notably to the dentate gyrus, superior colliculus, hippocampus, thalamus and piriform cortex. Staining was also observed in the retrosplenial and somatosensory cortex. The 3.0 kb t-PA promoter directed generalized and poorly defined expression to the cortex and hippocampus, while the 1.4 kb t-PA promoter directed expression selectively to the medial habenula. Intravenous administration of lipopolysaccharide into mice harbouring the 9.5 kb t-PA promoter resulted in an increase in reporter gene activity in the lateral orbital cortex and thalamus. Results of in vitro transfection experiments of NT2 cells with a series of t-PA promoter deletion constructs confirmed the presence of regulatory elements throughout the 9.5 kb promoter region. Finally, we describe a cis-acting element related to the NFAT recognition site that provides a protein-binding site and which may play a role in the selective expression of the 1.4 t-PA promoter in the medial habenula. These results indicate that elements between -3.0 and -9.5 kb of the t-PA promoter confer constitutive and inducible expression to specific regions of the CNS.

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Section: Lipopolysaccharide (Lps) Treatment Induces Lacz Expression Imentioning

confidence: 99%

Control elements between −9.5 and −3.0 kb in the human tissue‐type plasminogen activator gene promoter direct spatial and inducible expression to the murine brain

Schleuning²,

Michl³

et al. 2001

Eur J of Neuroscience

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“…Cerebral insulin expression has been observed in only one structure, the median habenular nucleus. Using double immunohistochemical staining, human insulin was shown to be colocalized in cholinergic habenular neurons ( Douhet et al . 1995 ).…”

Section: Introductionmentioning

confidence: 99%

Human insulin gene insertion in mice. Effects on the sleep–wake cycle?

Valatx

Douhet

Bucchini

1999

Journal of Sleep Research

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Recently, insulin synthesis and the presence of an insulin receptor have been demonstrated in the brain. Intracerebroventricular infusion of insulin causes a selective increase in the amount of slow-wave sleep. In the present study, the sleep-wake cycle of transgenic mice, with or without habenular neuronal expression of the human insulin gene, was studied to investigate the possible role of brain insulin as a sleep modulator. Slow-wave sleep duration was increased in those mice expressing human insulin in the habenula. However, it is possible that this effect was not due to expression of the insulin transgene, but to the genetic background of one of the parental strains (CBA) used for insertion of the transgene. Users of transgenic mice should be aware of this possibility and be cautious in interpreting results when hybrid embryos are used as transgene recipients.

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Manipulation of gene expression in the mammalian nervous system: application in the study of neurite outgrowth and neuroregeneration-related proteins

Holtmaat¹,

Oestreicher²,

Gispen³

et al. 1998

Brain Research Reviews

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Expression of a human insulin transgene in cholinergic neurons of the mouse medial habenula

Cited by 4 publications

References 30 publications

Control elements between −9.5 and −3.0 kb in the human tissue‐type plasminogen activator gene promoter direct spatial and inducible expression to the murine brain

Control elements between −9.5 and −3.0 kb in the human tissue‐type plasminogen activator gene promoter direct spatial and inducible expression to the murine brain

Human insulin gene insertion in mice. Effects on the sleep–wake cycle?

Manipulation of gene expression in the mammalian nervous system: application in the study of neurite outgrowth and neuroregeneration-related proteins

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