EMS-induced mutant frequency and spectrum in bone marrow of D6-2 transgenic mice

1998 ◽  
Vol 41 (3) ◽  
pp. 286-292
Author(s):  
Huaixing Li ◽  
Hua Yang ◽  
Jianxiu Li ◽  
Yiping Hu ◽  
Xiaopeng Wang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
Mutant Frequency ◽  
Induced Mutant

scholarly journals Bisecting GlcNAc structure is implicated in suppression of stroma-dependent haemopoiesis in transgenic mice expressing N-acetylglucosaminyltransferase III

1998 ◽  
Vol 331 (3) ◽  
pp. 733-742 ◽  
Author(s):  
Masafumi YOSHIMURA ◽  
Yoshito IHARA ◽  
Tetsuo NISHIURA ◽  
Yu OKAJIMA ◽  
Megumu OGAWA ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
Stromal Cells ◽  
Bone Marrow Cells ◽  
Adherent Cell ◽  
Wild Type ◽  
Spleen Cells ◽  
Bisecting Glcnac ◽  
Marrow Cells

Several sugar structures have been reported to be necessary for haemopoiesis. We analysed the haematological phenotypes of transgenic mice expressing β-1,4 N-acetylglucosaminyltransferase III (GnT-III), which forms bisecting N-acetylglucosamine on asparagine-linked oligosaccharides. In the transgenic mice, the GnT-III activity was elevated in bone marrow, spleen and peripheral blood and in isolated mononuclear cells from these tissues, whereas no activity was found in these tissues of wild-type mice. Stromal cells after long-term cultures of transgenic-derived bone marrow and spleen cells also showed elevated GnT-III activity, compared with an undetectable activity in wild-type stromal cells. As judged by HPLC analysis, lectin blotting and lectin cytotoxicity assay, bisecting GlcNAc residues were increased on both blood cells and stromal cells from bone marrow and spleen in transgenic mice. The transgenic mice displayed spleen atrophy, hypocellular bone marrow and pancytopenia. Bone marrow cells and spleen cells from transgenic mice produced fewer haemopoietic colonies. After lethal irradiation followed by bone marrow transplantation, transgenic recipient mice showed pancytopenia compared with wild-type recipient mice. Bone marrow cells from transgenic donors gave haematological reconstitution at the same level as wild-type donor cells. In addition, non-adherent cell production was decreased in long-term bone marrow cell cultures of transgenic mice. Collectively these results indicate that the stroma-supported haemopoiesis is compromised in transgenic mice expressing GnT-III, providing the first demonstration that the N-glycans have some significant roles in stroma-dependent haemopoiesis.

scholarly journals In vivo mutagenicity and mutation spectrum in the bone marrow and testes of B6C3F1 lacI transgenic mice following inhalation exposure to ethylene oxide

Mutagenesis ◽  
2004 ◽  
Vol 19 (3) ◽  
pp. 215-222 ◽  
Author(s):  
Leslie Recio ◽  
Maria Donner ◽  
Diane Abernethy ◽  
Linda Pluta ◽  
Ann‐Marie Steen ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
Ethylene Oxide ◽  
Inhalation Exposure ◽  
Mutation Spectrum ◽  
In Vivo Mutagenicity

Bone marrow derived macrophages from human CETP transgenic mice exhibit reduced phenotypic polarization to M1.

2021 ◽  
Vol 331 ◽  
pp. e72-e73
Author(s):  
K.G. Santana ◽  
F.E. Dantas ◽  
C.N. De Souza ◽  
O. Dominguez ◽  
E. Quintão ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice

scholarly journals Limitations of the use of GFP transgenic mice in bone marrow transplantation studies

2006 ◽  
Vol 47 (7) ◽  
pp. 1392-1393 ◽  
Author(s):  
Nancy Van Overstraeten-Schlögel ◽  
Marie Delgaudine ◽  
Yves Beguin ◽  
André Gothot
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Transplantation ◽  
Transgenic Mice ◽  
Marrow Transplantation

scholarly journals Syngeneic transplantation of hematopoietic stem cells that are genetically modified to express factor VIII in platelets restores hemostasis to hemophilia A mice with preexisting FVIII immunity

Blood ◽  
2008 ◽  
Vol 112 (7) ◽  
pp. 2713-2721 ◽  
Author(s):  
Qizhen Shi ◽  
Scot A. Fahs ◽  
David A. Wilcox ◽  
Erin L. Kuether ◽  
Patricia A. Morateck ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Transgenic Mice ◽  
Hematopoietic Stem Cells ◽  
Factor Viii ◽  
Hemophilia A ◽  
Genetically Modified ◽  
Hematopoietic Stem ◽  
Inhibitory Antibodies ◽  
Sublethal Irradiation

Abstract Although genetic induction of factor VIII (FVIII) expression in platelets can restore hemostasis in hemophilia A mice, this approach has not been studied in the clinical setting of preexisting FVIII inhibitory antibodies to determine whether such antibodies would affect therapeutic engraftment. We generated a line of transgenic mice (2bF8) that express FVIII only in platelets using the platelet-specific αIIb promoter and bred this 2bF8 transgene into a FVIIInull background. Bone marrow (BM) from heterozygous 2bF8 transgenic (2bF8tg+/−) mice was transplanted into immunized FVIIInull mice after lethal or sublethal irradiation. After BM reconstitution, 85% of recipients survived tail clipping when the 1100-cGy (myeloablative) regimen was used, 85.7% of recipients survived when 660-cGy (nonmyeloablative) regimens were used, and 60% of recipients survived when the recipients were conditioned with 440 cGy. Our further studies showed that transplantation with 1% to 5% 2bF8tg+/− BM cells still improved hemostasis in hemophilia A mice with inhibitors. These results demonstrate that the presence of FVIII-specific immunity in recipients does not negate engraftment of 2bF8 genetically modified hematopoietic stem cells, and transplantation of these hematopoietic stem cells can efficiently restore hemostasis to hemophilic mice with preexisting inhibitory antibodies under either myeloablative or nonmyeloablative regimens.

Abstract 49: Elevating Apolipoprotein A-I Levels Promotes Atherosclerosis Regression in Diabetic Mice by Inhibiting Proliferation of Bone Marrow Monocyte Precursors

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Tessa J Barrett ◽  
Emilie Distel ◽  
Yoscar Ogando ◽  
Yaritzy M Astudillo ◽  
Jianhua Liu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Transgenic Mice ◽  
Plasma Cholesterol ◽  
Atherosclerotic Lesion ◽  
Lipid Lowering ◽  
Diabetic Mice ◽  
Blood Monocytes ◽  
Post Surgery ◽  
Lesion Regression

Diabetes is a primary risk factor for cardiovascular diseases (CVD) and in clinical imaging studies is shown to impair the resolution of CVD, a process termed regression. We have also reported this failure of lesion regression in mouse models of diabetes, despite effective lipid lowering. This, in part, can be attributed to diabetes-driven monocytosis promoting continued monocyte infiltration into plaques. In non-diabetic settings apolipoprotein (apo) A-I and high-density lipoprotein (HDL) suppress leukocytosis and promote lesion regression. As low apoA-I/HDL is a typical feature of diabetic dyslipidemia this study aimed to establish whether raising apoA-I/HDL levels in vivo is an effective approach to reduce diabetes-driven leukocytosis and promote lesion regression. Aortic arches from hyperlipidemic Ldlr -/- mice were transplanted into WT, diabetic WT, and diabetic human apoA-I-overexpressing transgenic mice (transgenic mice have a 3-fold increase in HDL-cholesterol), and lesion composition assessed 2 weeks post-surgery. Following aortic transplantation into WT mice (i.e. normal lipid levels) we found regression, as assessed by change in plaque macrophage (mΦ) content relative to baseline control mice was achieved (68% mΦ reduction, P<0.001). Regression was impaired when aortas were transplanted into diabetic WT recipients (50% mΦ reduction, P<0.01). However, raising apoA-I/HDL levels in the setting of diabetes restored regression in diabetic mice (62% mΦ reduction, P<0.001). In vivo monocyte/mΦ trafficking analyses revealed that elevating apoA-I/HDL levels in diabetes improves atherosclerosis regression by reducing monocyte entry by 60% (P<0.01), and promoting mΦ egress from lesions (30% increase). We also found that greater apoA-I/HDL reduced blood monocytes by decreasing the proliferation of monocyte progenitors in the bone marrow (15-20% reduction, P<0.05), explaining, in part, how apoA-I/HDL promotes regression. Raising apoA-I/HDL levels promotes atherosclerotic lesion regression in diabetic mice. This may serve as a therapeutic strategy for patients with diabetes, who unlike WT mice, have reduced HDL levels and remain at an elevated risk for CVD despite effective plasma cholesterol lowering.

scholarly journals Fos-related antigen-1 transgenic mouse as a model for systemic sclerosis: A potential role of M2 polarization

2019 ◽  
Vol 4 (2) ◽  
pp. 137-148
Author(s):  
Hidekata Yasuoka ◽  
Yuen Yu Angela Tam ◽  
Yuka Okazaki ◽  
Yuichi Tamura ◽  
Koichi Matsuo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Systemic Sclerosis ◽  
Transgenic Mice ◽  
Pressure Gradient ◽  
Transgenic Mouse ◽  
Tricuspid Regurgitation ◽  
Mononuclear Cells ◽  
M2 Macrophages ◽  
Wild Type ◽  
M2 Polarization

Objectives: To investigate the systemic sclerosis–related phenotype in fos-related antigen-1 transgenic mice and its underlying mechanisms. Methods: Lung and skin sections of constitutive fos-related antigen-1 transgenic mice and wild-type mice were examined by tissue staining and immunohistochemistry. The tricuspid regurgitation pressure gradient was measured by transthoracic echocardiography with a Doppler technique. To assess the impact of fos-related antigen-1 expression on macrophage function, bone marrow–derived mononuclear cells were derived from mice that expressed fos-related antigen-1 under the control of doxycycline and wild-type littermates. These bone marrow–derived mononuclear cells were induced to differentiate into macrophages with or without doxycycline, and analyzed for gene and protein expression. Finally, lung explants obtained from systemic sclerosis patients and control donors were subjected to immunohistochemistry. Results: The lungs of fos-related antigen-1 transgenic mice showed excessive fibrosis of the interstitium and thickening of vessel walls, with narrowing lumen, in an age-dependent manner. The tricuspid regurgitation pressure gradient was significantly elevated in fos-related antigen-1 transgenic versus control mice. Increased dermal thickness and the loss of subdermal adipose tissue were also observed in the fos-related antigen-1 transgenic mice. These changes were preceded by a perivascular infiltration of mononuclear cells, predominantly consisting of alternatively activated or M2 macrophages. Overexpressing fos-related antigen-1 in bone marrow–derived mononuclear cell cultures increased the expression of M2-related genes, such as Il10, Alox15, and Arg1. Finally, fos-related antigen-1-expressing M2 macrophages were increased in the lung tissues of systemic sclerosis patients. Conclusions: The fos-related antigen-1 transgenic mouse serves as a genetic model of systemic sclerosis that recapitulates the major vascular and fibrotic manifestations of the lungs and skin in systemic sclerosis patients. M2 polarization mediated by the up-regulation of fos-related antigen-1 may play a critical role in the development of systemic sclerosis.

scholarly journals Transplantation of bone marrow cells from transgenic mice expressing the human MDR1 gene results in long-term protection against the myelosuppressive effect of chemotherapy in mice

Blood ◽  
1992 ◽  
Vol 79 (4) ◽  
pp. 1087-1093 ◽  
Author(s):  
GH Mickisch ◽  
I Aksentijevich ◽  
PV Schoenlein ◽  
LJ Goldstein ◽  
H Galski ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Multidrug Resistance ◽  
Transgenic Mice ◽  
Dose Escalation ◽  
Blot Analysis ◽  
Messenger Rna ◽  
Bone Marrow Cells ◽  
Selective Advantage ◽  
Mdr1 Gene ◽  
Human Mdr1

Abstract Many human cancers that are initially responsive to chemotherapy eventually fail to respond to treatment. For some drugs, dose escalation that may be required for a cure cannot be achieved because sensitive tissues such as bone marrow (BM) limit cytotoxic therapy. Approaches to prevent or circumvent BM toxicity are therefore a high priority of research on dose escalation protocols. In this study, we have transplanted BM cells from transgenic mice that constitutively express physiologic amounts of a functional human multidrug resistance (MDR1) cDNA to lethally irradiated C57BL/6 x SJL F1 mice (n = 36). From 6 weeks to 10 months after the transplant, all animals contained MDR1 DNA in spleen and BM specimens as indicated by Southern blot analysis, and expressed MDR1 messenger RNA in BM samples as detected by slot blot analysis. In addition, these animals were resistant to the myelosuppressive effect of doxorubicin, daunomycin, taxol, vinblastine, vincristine, etoposide, and actinomycin D, whereas control animals that were reconstituted with normal BM were drug sensitive. Finally, the chemoprotection afforded by the MDR1 gene could readily be reversed by adding chemosensitizers such as cyclosporin A and R-verapamil to chemotherapy. Hence, it appears that BM cells expressing the human MDR1 gene maintain this function after transplantation to host animals for a minimum of 10 months, and confer multidrug resistance to these BM recipients. This selective advantage conferred by expression of the MDR1 cDNA suggests a strategy for the use of MDR1 gene therapy in cancer chemotherapy and for the introduction of otherwise nonselectable genes into BM.

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