BAC Transgenic Mice and the GENSAT Database of Engineered Mouse Strains

To mimic Alzheimer’s disease, transgenic mice overexpressing the amyloid precursor protein (APP) were used in this study. We hypothesize that the neuroprotective effects of ETAS®50, a standardized extract of Asparagus officinalis stem produced by Amino Up Co., Ltd. (Sapporo, Japan), are linked to the inhibition of the apoptosis cascade through an enhancement of the stress-response proteins: heat shock proteins (HSPs). APP-overexpressing mice (double-transgenic APP and PS1 mouse strains with a 129s6 background), ages 6-8 weeks old, and weighing 20-24 grams were successfully bred in our laboratory. The animals were divided into 5 groups. APP-overexpressing mice and wild-type (WT) mice were pretreated with ETAS®50 powder (50% elemental ETAS and 50% destrin) at 200 mg/kg and 1000 mg/kg body weight. Saline, the vehicle for ETAS®50, was administered in APP-overexpressing mice and WT mice. ETAS®50 and saline were administered by gavage daily for 1 month. Cognitive assessments, using the Morris Water Maze, demonstrated that memory was recovered following ETAS®50 treatment as compared to nontreated APP mice. At euthanization, the brain was removed and HSPs, amyloid β, tau proteins, and caspase-3 were evaluated through immunofluorescence staining with the appropriate antibodies. Our data indicate that APP mice have cognitive impairment along with elevated amyloid β, tau proteins, and caspase-3. ETAS®50 restored cognitive function in these transgenic mice, increased both HSP70 and HSP27, and attenuated pathogenic level of amyloid β, tau proteins, and caspsase-3 leading to neuroprotection. Our results were confirmed with a significant increase in HSP70 gene expression in the hippocampus.

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Gene Dose–Dependent Maturation and Receptor Editing of B Cells Expressing Immunoglobulin (Ig)g1 or Igm/Igg1 Tail Antigen Receptors

Journal of Experimental Medicine ◽

10.1084/jem.191.6.1031 ◽

2000 ◽

Vol 191 (6) ◽

pp. 1031-1044 ◽

Cited By ~ 30

Author(s):

Sarah L. Pogue ◽

Christopher C. Goodnow

Keyword(s):

B Cells ◽

Transgenic Mice ◽

B Cell ◽

Copy Number ◽

Memory B Cells ◽

Mouse Strains ◽

Allelic Exclusion ◽

Antigen Receptors ◽

Cytoplasmic Domains ◽

Transgene Copy Number

Conserved differences between the transmembrane and cytoplasmic domains of membrane immunoglobulin (Ig)M and IgG may alter the function of antigen receptors on naive versus memory B cells. Here, we compare the ability of these domains to signal B cell allelic exclusion and maturation in transgenic mice. A lysozyme-binding antibody was expressed in parallel sets of mice as IgM, IgG1, or a chimeric receptor with IgM extracellular domains and transmembrane/cytoplasmic domains of IgG1. Like IgM, the IgG1 or chimeric IgM/G receptors triggered heavy chain allelic exclusion and supported development of mature CD21+ B cells. Many of the IgG or IgM/G B cells became CD21high and downregulated their IgG and IgM/G receptors spontaneously, resembling memory B cells and B cells with mutations that exaggerate B cell antigen receptor signaling. Unlike IgM-transgenic mice, “edited” B cells that carry non–hen egg lysozyme binding receptors preferentially accumulated in IgG and IgM/G mice. This was most extreme in lines with the highest transgene copy number and diminished in variant offspring with fewer copies. The sensitivity of B cell maturation to transgene copy number conferred by the IgG transmembrane and cytoplasmic domains may explain the diverse phenotypes found in other IgG-transgenic mouse strains and may reflect exaggerated signaling.

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Correction: Expression Analysis of CB2-GFP BAC Transgenic Mice

PLoS ONE ◽

10.1371/journal.pone.0145472 ◽

2015 ◽

Vol 10 (12) ◽

pp. e0145472

Author(s):

Anne-Caroline Schmöle ◽

Ramona Lundt ◽

Benjamin Gennequin ◽

Hanna Schrage ◽

Eva Beins ◽

...

Keyword(s):

Transgenic Mice ◽

Expression Analysis ◽

Bac Transgenic Mice

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Tissue-specific and neural activity-regulated expression of human BDNF gene in BAC transgenic mice

BMC Neuroscience ◽

10.1186/1471-2202-10-68 ◽

2009 ◽

Vol 10 (1) ◽

pp. 68 ◽

Cited By ~ 21

Author(s):

Indrek Koppel ◽

Tamara Aid-Pavlidis ◽

Kaur Jaanson ◽

Mari Sepp ◽

Priit Pruunsild ◽

...

Keyword(s):

Transgenic Mice ◽

Neural Activity ◽

Bdnf Gene ◽

Tissue Specific ◽

Regulated Expression ◽

Bac Transgenic Mice

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Prion Protein Expression Differences in Microglia and Astroglia Influence Scrapie-Induced Neurodegeneration in the Retina and Brain of Transgenic Mice

Journal of Virology ◽

10.1128/jvi.00865-07 ◽

2007 ◽

Vol 81 (19) ◽

pp. 10340-10351 ◽

Cited By ~ 31

Author(s):

Lisa Kercher ◽

Cynthia Favara ◽

James F. Striebel ◽

Rachel LaCasse ◽

Bruce Chesebro

Keyword(s):

Transgenic Mice ◽

Prion Protein ◽

Microglial Activation ◽

Prion Diseases ◽

Cell Types ◽

Mouse Strains ◽

Activation Markers ◽

Activated Microglia ◽

Morphological Criteria ◽

Scrapie Infection

ABSTRACT Activated microglia and astroglia are known to be involved in a variety of neurodegenerative diseases, including prion diseases. In the present experiments, we studied activation of astroglia and microglia after intraocular scrapie infection in transgenic mice expressing prion protein (PrP) in multiple cell types (tg7 mice) or in neurons only (tgNSE mice). In this model, scrapie infection and protease-resistant PrP deposition occurs in the retinas of both strains of mice, but retinal degeneration is observed only in tg7 mice. Our results showed that the retinas of tg7 and tgNSE mice both had astroglial activation with increased chemokine expression during the course of infection. However, only tg7 retinas exhibited strong microglial activation compared to tgNSE retinas, which showed little microglial activation by biochemical or morphological criteria. Therefore, microglial PrP expression might be required for scrapie-induced retinal microglial activation and damage. Furthermore, microglial activation preceded retinal neurodegeneration in tg7 mice, suggesting that activated microglia might contribute to the degenerative process, rather than being a response to the damage. Surprisingly, brain differed from retina in that an altered profile of microglial activation markers was upregulated, and the profiles in the two mouse strains were indistinguishable. Microglial activation in the brain was associated with severe brain vacuolation and neurodegeneration, leading to death. Thus, retinal and brain microglia appeared to differ in their requirements for activation, suggesting that different activation pathways occur in the two tissues.

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Hyperglycemia and impaired glucose tolerance in IGF binding protein-1 transgenic mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.4.e565 ◽

1996 ◽

Vol 270 (4) ◽

pp. E565-E571 ◽

Cited By ~ 6

Author(s):

K. Rajkumar ◽

S. T. Dheen ◽

L. J. Murphy

Keyword(s):

Growth Factors ◽

Glucose Tolerance ◽

Transgenic Mice ◽

Impaired Glucose Tolerance ◽

Serum Insulin ◽

Mouse Strains ◽

Wild Type ◽

Glucose Response ◽

Glucose Ratio ◽

Glucose Challenge

The insulin-like growth factors (IGFs) are present in the serum in association with high-affinity binding proteins (IGFBPs), which limit the hypoglycemic insulin-like actions of these growth factors. By utilizing the mouse phosphoglycerate kinase promoter to drive a rat genomic fragment, we developed three transgenic mouse strains that overexpressed IGFBP-1. Homozygous offspring demonstrated fasting hyperglycemia. The blood glucose values were 4.97 +/- 0.37, 4.57 +/- 0.33, and 5.58 +/- 0.50 mM for transgenic mice compared with 3.33 +/- 0.19 mM (mean +/- SE, P < 0.05) for the wild-type mice. The transgenic mice had more marked hyperglycemia after an intraperitoneal glucose challenge. The fasting serum insulin levels were significantly elevated in the transgenic mice; however, the insulin-to-glucose ratio was only modestly elevated in the fasting state and fell after a glucose challenge. Islet size and number were significantly increased; however, pancreatic insulin content was reduced (P < 0.05) compared with that of wild-type mice. The glucose response to subcutaneous insulin was similar in transgenic and wild-type mice. These data demonstrate that constitutive overexpression of IGFBP-1 results in impaired glucose tolerance with normal insulin sensitivity.

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