Somatostatin sst2 receptor knock-out mice: localisation of sst1–5 receptor mRNA and binding in mouse brain by semi-quantitative RT–PCR, in situ hybridisation histochemistry and receptor autoradiography

Hannon, Jason P.; Petrucci, Cristina; Fehlmann, Dominique; Viollet, Cécile; Epelbaum, Jacques; Hoyer, Daniel

doi:10.1016/s0028-3908(01)00186-1

Cited by 54 publications

(55 citation statements)

References 48 publications

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“…The uninjected hemispheres showed no red fluorescence, and numerous red-fluorescing mKate2-transduced cells were observed along the lower length of the needle track in the VSV G-LVinjected mouse, whereas the needle track of the Sst-RBS-LVinjected brain showed very few red-fluorescing cells, but a burst of transduction at the end of the needle track in the subthalamic nucleus was apparent (preliminary data not shown). The regions directly above the subthalamic nucleus are reportedly negative for SSTR (18,25,34) but are positive for VSV G receptors (30). Interpretation of this preliminary result must be cautious, as further extensive in vivo studies are needed to determine which cell types were transduced and whether in vivo targeting to SSTR occurred.…”

Section: Discussionmentioning

confidence: 88%

“…In vivo SSTR are abundant in a number of clinically relevant target tissues, specifically, the subthalamic nucleus, striatum, substantia nigra, amygdala, and hippocampus in the brain, the endocrine glands of the pancreas, an unknown cell type in the lungs, and the ileum, but not in other tissues (18,25,34,51). However, the primary cells from these SSTR-positive tissues are extremely difficult to culture, and some, like cells from the subthalamic nucleus, have not been cultured.…”

Section: Discussionmentioning

confidence: 99%

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Targeted Entry via Somatostatin Receptors Using a Novel Modified Retrovirus Glycoprotein That Delivers Genes at Levels Comparable to Those of Wild-Type Viral Glycoproteins

Li¹,

Ryu

Krueger³

et al. 2012

J Virol

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Here we report a novel viral glycoprotein created by replacing a natural receptor-binding sequence of the ecotropic Moloney murine leukemia virus envelope glycoprotein with the peptide ligand somatostatin. This new chimeric glycoprotein, which has been named the Sst receptor binding site (Sst-RBS), gives targeted transduction based on three criteria: (i) a gain of the use of a new entry receptor not used by any known virus; (ii) targeted entry at levels comparable to gene delivery by wild-type ecotropic Moloney murine leukemia virus and vesicular stomatitis virus (VSV) G glycoproteins; and (iii) a loss of the use of the natural ecotropic virus receptor. Retroviral vectors coated with Sst-RBS gained the ability to bind and transduce human 293 cells expressing somatostatin receptors. Their infection was specific to target somatostatin receptors, since a synthetic somatostatin peptide inhibited infection in a dose-dependent manner and the ability to transduce mouse cells bearing the natural ecotropic receptor was effectively lost. Importantly, vectors coated with the Sst-RBS glycoprotein gave targeted entry of up to 1 ؋ 10 6 transducing U/ml, a level comparable to that seen with infection of vectors coated with the parental wild-type ecotropic Moloney murine leukemia virus glycoprotein through the ecotropic receptor and approaching that of infection of VSV G-coated vectors through the VSV receptor. To our knowledge, this is the first example of a glycoprotein that gives targeted entry of retroviral vectors at levels comparable to the natural capacity of viral envelope glycoproteins.

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Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Targeted Entry via Somatostatin Receptors Using a Novel Modified Retrovirus Glycoprotein That Delivers Genes at Levels Comparable to Those of Wild-Type Viral Glycoproteins

Li¹,

Ryu

Krueger³

et al. 2012

J Virol

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“…In SSTR2 KO the staining pattern did not differ from that of WT mice [30]. In addition, no major compensatory regulation of SST or individual SSTRs has been described as a consequence of the genetic deletion of SSTR1 or SSTR2 in specific brain regions [37]. In the retina, recently major alterations of SST content were demonstrated as a consequence of SSTR1 or SSTR2 deletion [38].…”

Section: Expression Of Somatostatin Receptors In Cochlea Of Knock Outmentioning

confidence: 89%

Targeting the somatostatin receptors as a therapeutic approach for the preservation and protection of the mammalian cochlea from excitotoxicity

Radojević¹,

Brand²,

Levano³

et al. 2013

Translational Neuroscience

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The neuropeptide somatostatin (SST) is an important modulator of neurotransmission in the central nervous system (CNS) and binds to G-protein-coupled receptors (SSTR1-5) on target cells. Little is known about the expression and function of the somatostatinergic system in the mammalian cochlea. We analyzed the expression of SSTR1-SSTR5 in the immature mammalian cochlea. The peak in the expression of SSTR1 and SSTR2 at mRNA and protein level is around the onset of hearing to airborne sound, at postnatal day (P)14. This suggests their involvement in the maturation of the mammalian cochlea. We demonstrated that all five receptors are expressed in the inner hair cells (IHC) and outer hear cells (OHC) as well as in defined supporting cells of the organ of Corti (OC) in the adult mouse cochlea. A similar expression of the SSTRs in the IHC and OHC was found in cultivated P6 mouse OC explants as well as in neuroepithelial cell culture. In order to learn more about the regulation of SSTRs, we used mice with either a deletion of SSTR1, SSTR2 or SSTR1/SSTR2 double knock out (DKO). In DKO mice, SSTR5 was up-regulated and SSTR3 and SSTR4 were down regulated. These findings provide evidence of a compensatory regulation in the mammalian cochlea as a consequence of a receptor subtype deletion. In addition, we observed reduced levels of phospho-Akt and total-Akt in SSTR1 KO and DKO mice as compared to wild type (WT) mice. Akt is likely to be involved in hair cell survival. Most importantly, we found improved hair cell survival in somatostatin and octreotide treated OC explants that had been exposed to gentamicin compared to those explants exposed to gentamicin alone. These findings propose that the somatostatinergic system within the cochlea may have neuroprotective properties.

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“…In contrast, the same length of needle track in the Sst-RBS LV injected mouse showed very few red fluorescent cells but a burst of transduction was observed at the end of the needle track in the region of the SN (Figure 5-1C). The area directly above the SN is reportedly negative for SSTR expression [88,89,92], however the cellular receptor recognizing VSV G is present throughout these regions [93]. This provides proof principle that Sst-RBS LV does indeed transduce murine brain cells and may represent targeted transduction of SSTR positive cells since a majority of red fluorescence was observed at the end of the needletrack in a region reported to express SSTR [88] while VSV G LV transduced cells in both SSTR expressing and non-expressing regions.…”

Section: Proof Of Principle For In Vivo Gene Transduction By Sst-rbs mentioning

confidence: 99%

“…Historically, investigations into the expression of SSTR in the rat and mouse brain have been confined in situ hybridization to localize SSTR subtype mRNA expression or autoradiography using radiolabeled synthetic ligands [88,92]. More recently, rat models have been used to directly address the level of SSTR surface expression in brain cells with subtype specific antibodies [89].…”

Section: Sstr-2 Expression In the Murine Brainmentioning

confidence: 99%

In vitro and In vivo Characterization of the Infection Efficiency of a Modified Retrovirus Envelope Glycoprotein for Targeting Gene Transduction

Krueger¹

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Somatostatin sst2 receptor knock-out mice: localisation of sst1–5 receptor mRNA and binding in mouse brain by semi-quantitative RT–PCR, in situ hybridisation histochemistry and receptor autoradiography

Cited by 54 publications

References 48 publications

Targeted Entry via Somatostatin Receptors Using a Novel Modified Retrovirus Glycoprotein That Delivers Genes at Levels Comparable to Those of Wild-Type Viral Glycoproteins

Targeted Entry via Somatostatin Receptors Using a Novel Modified Retrovirus Glycoprotein That Delivers Genes at Levels Comparable to Those of Wild-Type Viral Glycoproteins

Targeting the somatostatin receptors as a therapeutic approach for the preservation and protection of the mammalian cochlea from excitotoxicity

In vitro and In vivo Characterization of the Infection Efficiency of a Modified Retrovirus Envelope Glycoprotein for Targeting Gene Transduction

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