Cloning and expression of the neuromedin B receptor and the third subtype of bombesin receptor genes in the mouse

Ohki‐Hamazaki, Hiroko; Wada, Etsuko; Matsui, Kyoko; Wada, Keiji

doi:10.1016/s0006-8993(97)00380-6

Cited by 70 publications

(83 citation statements)

References 22 publications

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“…In contrast to GRPR and NMBR, BRS-3 is almost exclusively expressed in the brain and spinal cord of mice. 5 In brain, BRS-3 is dominantly expressed in hypothalamic nuclei including the paraventricular, arcuate and dorsomedial nuclei. 5 These nuclei are known to be involved in the regulation of the autonomic nervous system and in endocrine function.…”

Section: Brs-3 Deficient Micementioning

confidence: 99%

“…5 In brain, BRS-3 is dominantly expressed in hypothalamic nuclei including the paraventricular, arcuate and dorsomedial nuclei. 5 These nuclei are known to be involved in the regulation of the autonomic nervous system and in endocrine function. Since gross anatomical changes were not observed in the hypothalamic region of BRS-3 deficient mice, BRS-3 deficiency is likely to cause functional but not morphological alterations in the hypothalamus.…”

Section: Brs-3 Deficient Micementioning

confidence: 99%

“…Distinct distributions of bombesin receptor subtypes in various tissues suggest independent roles of the receptors in such biological responses. 2,5 We have generated both GRPR and BRS-3 deficient mice in an effort to determine in vivo the function of these receptors. 6,7 …”

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Bombesin, obesity, and social behavior

Wada

Watase

et al. 1998

Mol Psychiatry

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The bombesin system has not been very well characterized in the brain. This may be due to a lack of specific antagonists or agonists or to the diversity of physiological effects of bombesin. Bombesin receptors are phylogenetically most related to endothelin receptors whose importance is well-known. Our studies on bombesin receptor knock-out mice indicate the necessity and potential fruitfulness of further efforts to examine in detail the role of bombesin in brain function.

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Section: Brs-3 Deficient Micementioning

confidence: 99%

Section: Brs-3 Deficient Micementioning

confidence: 99%

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Bombesin, obesity, and social behavior

Wada

Watase

et al. 1998

Mol Psychiatry

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“…4,5 BN-like peptides and their receptors are widely distributed in the mammalian CNS and modulate many aspects of behavior such as spontaneous activity and feeding behavior, as well as learning and memory. 6-9 We previously produced three strains of BN-like peptide receptor knockout mice using a gene targeting strategy.…”

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confidence: 99%

“…2,3 These peptides exert their effects by binding to G-protein coupled receptors such as the GRP receptor (GRP-R), the NMB receptor (NMB-R), and the BN receptor subtype-3 (BRS-3) for which no specific endogenous ligand(s) has yet been identified. 4,5 BN-like peptides and their receptors are widely distributed in the mammalian CNS and modulate many aspects of behavior such as spontaneous activity and feeding behavior, as well as learning and memory. [6][7][8][9] We previously produced three strains of BN-like peptide receptor knockout mice using a gene targeting strategy.…”

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Role of bombesin (BN)-like peptides/receptors in emotional behavior by comparison of three strains of BN-like peptide receptor knockout mice

et al. 2002

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Keywords: gastrin-releasing peptide receptor (GRP-R); bombesin receptor subtype-3 (BRS-3); neuromedin B receptor (NMB-R); light-dark (L-D) box test; elevated plus maze test; anxiety; emotion; knockout mice Bombesin (BN)-like peptides are involved in the regulation of a wide variety of behaviors, such as spontaneous activity and feeding. We assessed the role of BN-like peptides/receptors in emotional and/or anxietyrelated behavior using three strains of knockout mice, each deficient in a single BN-like peptide receptor (gastrin-releasing peptide receptor, bombesin receptor subtype-3, or neuromedin B receptor). Two representative behavioral paradigms, the light-dark (L-D) box test and the elevated plus maze test, were chosen for this purpose. In these two tests, the level of anxiety can be measured as the preference for exploring the light box, or the length of time spent in the open arms, respectively. By conventional parameters, the only significant finding was that BRS-3-deficient mice exhibited a longer duration of remaining in the open arms compared to the wild-type cohort (P Ͻ 0.01). However, analyses of risk assessment behavior revealed that BRS-3-deficient mice exhibited increased 'stretched attend posture' behavior (P Ͻ 0.01, compared to wild-type mice in both the L-D box and elevated plus maze tests) while NMB-Rdeficient mice exhibited decreased behavior (P Ͻ 0.05, compared to wild-type mice in both tests). These results suggest that BN-like peptides/receptors may play a role in modulating emotion including some forms of anxiety (eg, risk assessment behavior). Further, we found that the type of emotional behavior to which each of the peptide/receptor pathways contributes can be clearly specified. Molecular Psychiatry (2002) 7, 113-117. DOI: 10.1038/ sj/mp/4000974 Bombesin (BN) was originally purified from the skin of the European frog (Bombina bombina), 1 while the BNlike peptides gastrin-releasing peptide (GRP) and neuromedin B (NMB) were purified from mammalian tissues.2,3 These peptides exert their effects by binding to G-protein coupled receptors such as the GRP receptor (GRP-R), the NMB receptor (NMB-R), and the BN receptor subtype-3 (BRS-3) for which no specific endogenous ligand(s) has yet been identified. 4,5 BN-like peptides and their receptors are widely distributed in the mammalian CNS and modulate many aspects of behavior such as spontaneous activity and feeding behavior, as well as learning and memory. 6-9 We previously produced three strains of BN-like peptide receptor knockout mice using a gene targeting strategy. The resulting GRP-R-, NMB-R-and BRS-3-deficient mice were used in studies designed to clarify and distinguish the functional properties of BN-like peptides. These knockout mice exhibit unique phenotypes, such as elevated spontaneous activity and non-aggressive social behaviors in GRP-R-deficient mice.10-12 BRS-3-deficient mice exhibit moderate hyperphagia and obesity, 13 altered taste-related behaviors, 14 and decreased social behavior. 15 However, no behavioral phenotype has yet...

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Promoter methylation and transgene copy numbers predict unstable protein production in recombinant chinese hamster ovary cell lines

Osterlehner

Simmeth

Göpfert

2011

Biotech & Bioengineering

110

112

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Mammalian cell lines for recombinant protein production need to maintain productivity over extended cultivation times. Long-term stability studies are time and resource intensive, but are widely performed to identify and eliminate unstable candidates during cell line development. Production instability of manufacturing cell lines can be associated with methylation and silencing of the heterologous promoter. We have identified CpG dinucleotides within the human cytomegalovirus major immediate early promoter/enhancer (hCMV-MIE) that are frequently methylated in unstable antibody-producing Chinese hamster ovary (CHO) cell lines. We have established methylation-specific real-time qPCR for the rapid and sensitive measurement of hCMV-MIE methylation in multiple cell lines and provide evidence that hCMV-MIE methylation and transgene copy numbers can be used as early markers to predict production instability of recombinant CHO cell lines. These markers should provide the opportunity to enrich stable producers early in cell line development and allow developers to put more emphasis on other criteria, such as product quality and bioprocess robustness.

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Cloning and expression of the neuromedin B receptor and the third subtype of bombesin receptor genes in the mouse

Cited by 70 publications

References 22 publications

Bombesin, obesity, and social behavior

Bombesin, obesity, and social behavior

Role of bombesin (BN)-like peptides/receptors in emotional behavior by comparison of three strains of BN-like peptide receptor knockout mice

Promoter methylation and transgene copy numbers predict unstable protein production in recombinant chinese hamster ovary cell lines

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