16. Physiological effects of IDH1 loss-of-function on Chondrocyte Differentiation through Hedgehog Pathway upregulation

2018 ◽  
Author(s):  
Cassie Tyson
Keyword(s):  
Developmental Stages ◽  
Hedgehog Pathway ◽  
Chondrocyte Differentiation ◽  
Loss Of Function ◽  
Wild Type ◽  
Phenotypic Analysis ◽  
Growth Plate Chondrocytes ◽  
Idh Mutations ◽  
Cartilage Tumors ◽  
Deficient Mice

Cartilage tumors are the most common and terminal primary neoplasms in bone. Physiologically, bones formed through endochondral ossification are regulated by the Hedgehog pathway and Parathyroid hormone-like hormone feedback loop. The upregulation of the infamous Hedgehog pathway has been demonstrated in several non-cartilaginous neoplasms. Recently, frequent mutational events of isocitrate dehydrogenase1 (IDH1) were identified in cartilage tumors. In other neoplasms, IDH mutations produces an oncometabolite that can promote HIF1a activation, contributing to tumorigenesis. Currently, the role of IDH1 mutations in cartilage tumors remain unknown. Investigating the physiological aspect of IDH1proves useful in identifying novel therapeutic targets for cartilage tumors. IDH1 deficient and wild-type littermates, were harvested for forelimbs and hindlimbs at various developmental stages for phenotypic analysis via hematoxylin and eosin staining. Histological analysis demonstrated IDH1 homozygous deficient mice at embryonic stages exhibited dwarfism and an elongated layer of hypertrophic chondrocytes. This was verified via immunohistochemistry Type 10 Collagen staining and Quantitative PCR (qPCR) using the chondrocyte terminal differentiation marker Col10a1. Whole skeletons of IDH1 deficient mice were subjected to skeletal double staining which demonstrated delayed mineralization of underdeveloped IDH1 deficient mice contrasted with wild-type littermates. qPCR was performed to examine the status of chondrocyte differentiation through the Hedgehog pathway in cultured primarymouse growth plate chondrocytes. Interestingly, IDH1 deficient non-neoplastic cells revealed significant upregulation of Hedgehog target molecules in IDH1 deficient chondrocytes. As a result, the loss-offunction of IDH1 was identified as a potential impairment of chondrocyte differentiation and a factor towards chondrocyte tumorgenisis.

Generation of a BCR-ABL-Induced Leukemia Model in Osteopontin-Deficient Mice.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1438-1438
Author(s):  
Stephane Flamant ◽  
Martine Guillier ◽  
Marie Laure Bonnet ◽  
Ali G. Turhan
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Cell Line ◽  
Leukemic Cells ◽  
Cell Phenotype ◽  
Wild Type ◽  
Spleen Cells ◽  
Phenotypic Analysis ◽  
Deficient Mice

Abstract Osteopontin (OPN) is a secreted phoshoprotein playing multiple roles in cell migration, apoptosis and angiogenesis with evidence of increased expression in several types of epithelial tumors. Recently, OPN has also been shown to be a key regulator of the migration of hematopoietic stem cells towards the osteoblastic niche where it participates to the maintenance of the quiescence of stem cells after binding to integrins. We have previously shown that OPN is upregulated by BCR-ABL in a tyrosine-kinase-dependent manner in a TET-regulated BCR-ABL expressing cell line. To further study the potential role of OPN in BCR-ABL-associated leukemogenesis, we have used a retrovirus mediated BCR-ABL gene transfer strategy in OPN-deficient mice (OPN−/−). Bone marrow stem cells were harvested from OPN−/− and wild type OPN+/+ (C57Bl/6) mice after 5-FU treatment at day-5 and retrovirally transduced by a MIGR-p210 BCR-ABL vector in the presence of cytokines for 3 days. Retrovirally transduced marrow cells were transplanted into lethally irradiated OPN−/− mice in the presence of appropriate irradiation controls. Transplanted animals were followed regularly by blood counts, appearance of clinical disease and the results were compared to those obtained in OPN+/+ mice transplanted in the same conditions. In preliminary experiments, we have established that BCR-ABL-transduced OPN+/+ marrow can generate leukaemia in the background of OPN−/− mice with similar efficiencies (n=3) as in the background of OPN+/+ mice (n=3). In following experiments we have observed excessive mortality after irradiation (9–9.5 Gys) and established the optimal protocol pour induction of leukaemia in OPN−/− mice transplanted with OPN−/− cells. We have found that co-transplantation of 5.104 retrovirally transduced BM cells in the presence of 1.5 105 untransduced bone marrow allows reproducibly leukemia induction. The majority of OPN−/− mice (20/24, n=2 experiments) transplanted by the use of this protocol developed hyperleucocytosis between day 21–35 after transplantation. The latency of leukaemia did not differ between wild type and OPN−/− animals. At the time of sacrifice, all mice were found to have splenomegaly (500–950 mg). Both marrow and spleen cells had massive infiltration with GFP+ cells (40–80 %, marrow; 40–90%, spleen). At phenotypic analysis, OPN−/− leukemic cells were found to express at variable degrees Gr1, CD11b, Ter119, CD19, suggesting the establishment of a multilineage disease in the background of OPN−/− marrow. The phenotypic analysis leukemic cells from OPN+/+ mice was found to be similar. Culture of spleen cells from of a leukemic OPN−/− mouse gave rise to a GFP+ cell line expressing c-kit (97%) with negativity of Gr1, B220, Ter119 expression, suggesting its mast cell phenotype. Interestingly, this cell line has exquisite sensitivity to imatinib mesylate, the cytotoxicity of which is reduced by IL-3 but not by stem cell factor. In summary, these results demonstrate that OPN, a transcriptional target of BCR-ABL oncogene, is not required for BCR-ABL-induced murine leukemogenesis. It remains to be determined if it plays a role in the stem cell quiescence of BCR-ABL-expressing primitive cells in the osteoblastic niche and their resistance to BCR-ABL-targeted therapies. The OPN−/− murine CML modelthat we have established will be used to explore these questions as well as the homing potential of leukemic cells in the presence or in the absence of OPN.

scholarly journals Molecular and Phenotypic Analysis of 25 Recessive, Homozygous-Viable Alleles at the Mouse agouti Locus

Genetics ◽  
2002 ◽  
Vol 160 (2) ◽  
pp. 659-674
Author(s):  
Rosalynn J Miltenberger ◽  
Kazumasa Wakamatsu ◽  
Shosuke Ito ◽  
Richard P Woychik ◽  
Liane B Russell ◽  
...  
Keyword(s):  
Loss Of Function ◽  
Wild Type ◽  
Allelic Series ◽  
Phenotypic Analysis ◽  
Protein Coding ◽  
Agouti Locus ◽  
Expression Control ◽  
Gene Expression Control ◽  
Specific Locus

Abstract Agouti is a paracrine-acting, transient antagonist of melanocortin 1 receptors that specifies the subapical band of yellow on otherwise black hairs of the wild-type coat. To better understand both agouti structure/function and the germline damage caused by chemicals and radiation, an allelic series of 25 recessive, homozygous-viable agouti mutations generated in specific-locus tests were characterized. Visual inspection of fur, augmented by quantifiable chemical analysis of hair melanins, suggested four phenotypic categories (mild, moderate, umbrous-like, severe) for the 18 hypomorphs and a single category for the 7 amorphs (null). Molecular analysis indicated protein-coding alterations in 8 hypomorphs and 6 amorphs, with mild-moderate phenotypes correlating with signal peptide or basic domain mutations, and more devastating phenotypes resulting from C-terminal lesions. Ten hypomorphs and one null demonstrated wild-type coding potential, suggesting that they contain mutations elsewhere in the ≥125-kb agouti locus that either reduce the level or alter the temporal/spatial distribution of agouti transcripts. Beyond the notable contributions to the field of mouse germ cell mutagenesis, analysis of this allelic series illustrates that complete abrogation of agouti function in vivo occurs most often through protein-coding lesions, whereas partial loss of function occurs slightly more frequently at the level of gene expression control.

scholarly journals Upregulation of L-type calcium channels in colonic inhibitory motoneurons of P/Q-type calcium channel-deficient mice

2016 ◽  
Vol 311 (4) ◽  
pp. G763-G774 ◽  
Author(s):  
Eileen Rodriguez-Tapia ◽  
Alberto Perez-Medina ◽  
Xiaochun Bian ◽  
James J. Galligan
Keyword(s):  
Neuromuscular Transmission ◽  
Ex Vivo ◽  
Fecal Pellet ◽  
Colonic Motility ◽  
Circular Muscle ◽  
Resting Membrane Potential ◽  
Loss Of Function ◽  
Wild Type ◽  
Deficient Mice

Enteric inhibitory motoneurons use nitric oxide and a purine neurotransmitter to relax gastrointestinal smooth muscle. Enteric P/Q-type Ca2+ channels contribute to excitatory neuromuscular transmission; their contribution to inhibitory transmission is less clear. We used the colon from tottering mice ( tg/tg, loss of function mutation in the α1A pore-forming subunit of P/Q-type Ca2+ channels) to test the hypothesis that P/Q-type Ca2+ channels contribute to inhibitory neuromuscular transmission and colonic propulsive motility. Fecal pellet output in vivo and the colonic migrating motor complex (ex vivo) were measured. Neurogenic circular muscle relaxations and inhibitory junction potentials (IJPs) were also measured ex vivo. Colonic propulsive motility in vivo and ex vivo was impaired in tg/tg mice. IJPs were either unchanged or somewhat larger in tissues from tg/tg compared with wild-type (WT) mice. Nifedipine (L-type Ca2+ channel antagonist) inhibited IJPs by 35 and 14% in tissues from tg/tg and WT mice, respectively. The contribution of N- and R-type channels to neuromuscular transmission was larger in tissues from tg/tg compared with WT mice. The resting membrane potential of circular muscle cells was similar in tissues from tg/tg and WT mice. Neurogenic relaxations of circular muscle from tg/tg and WT mice were similar. These results demonstrate that a functional deficit in P/Q-type channels does not alter propulsive colonic motility. Myenteric neuron L-type Ca2+ channel function increases to compensate for loss of functional P/Q-type Ca2+ channels. This compensation maintains inhibitory neuromuscular transmission and normal colonic motility.

scholarly journals Fas and Fas Ligand Interactions Suppress Melanoma Lung Metastasis

1998 ◽  
Vol 188 (9) ◽  
pp. 1717-1723 ◽  
Author(s):  
Laurie B. Owen-Schaub ◽  
Kenneth L. van Golen ◽  
Laurie L. Hill ◽  
Janet E. Price
Keyword(s):  
Fas Ligand ◽  
Direct Evidence ◽  
Lung Metastases ◽  
Metastatic Tumor ◽  
Metastatic Progression ◽  
Loss Of Function ◽  
Wild Type ◽  
Metastatic Phenotype ◽  
Ligand Interactions ◽  
Deficient Mice

Apoptosis induced by Fas (CD95) ligation is frequently lost during tumor progression; however, there is no direct evidence to support an association of Fas loss-of-function with metastatic tumor behavior. To determine whether Fas loss-of-function is critical for acquisition of the metastatic phenotype, we have compared the ability of Fas-sensitive K1735 murine melanomas to form spontaneous lung metastases in wild-type and Fas ligand–deficient mice. Fas-sensitive melanoma clones are highly tumorigenic but rarely metastatic in wild-type syngeneic mice. However, in Fas ligand–deficient mice, both the incidence and number of metastases are increased. These findings provide the first evidence that Fas–Fas ligand interactions can suppress metastasis and that tumor Fas loss-of-function may be causally linked to metastatic progression.

scholarly journals Altered phenotype in LMAN1-deficient mice with low levels of residual LMAN1 expression

2020 ◽  
Vol 4 (22) ◽  
pp. 5635-5643
Author(s):  
Lesley A. Everett ◽  
Rami N. Khoriaty ◽  
Bin Zhang ◽  
David Ginsburg
Keyword(s):  
Human Subjects ◽  
Coagulation Factor ◽  
Coagulation Factors ◽  
Factor V ◽  
Mrna Levels ◽  
Loss Of Function ◽  
Wild Type ◽  
Cargo Proteins ◽  
Alpha 1 Antitrypsin ◽  
Deficient Mice

Abstract Combined deficiency of coagulation factors V and VIII (F5F8D) is an autosomal recessive bleeding disorder caused by loss-of-function mutations in either LMAN1 or MCFD2. The latter genes encode 2 components of a mammalian cargo receptor that facilitates secretion of coagulation factor V (FV) and factor VIII (FVIII) from the endoplasmic reticulum (ER) to the Golgi via coat protein complex II vesicles. F5F8D patients exhibit FV and FVIII levels that are ∼10% to 15% of normal. We report herein a comparative analysis for a series of murine Lman1 alleles. Consistent with previous reports, mice completely deficient in LMAN1 (Lman1−/−) exhibit ∼50% FV and FVIII levels. In contrast, mice carrying a hypomorphic Lman1 allele (Lman1cgt/cgt) that expresses ∼6% to 8% of wild-type Lman1 mRNA levels exhibit intermediate plasma FV and FVIII reductions (∼70% of wild-type levels). Lman1−/− mice exhibit ER accumulation of another LMAN1 cargo, alpha-1 antitrypsin (A1AT), with an intermediate level of A1AT ER retention observed in Lman1cgt/cgt mice. Finally, the previously reported strain-specific, partially penetrant, perinatal lethality of LMAN1-deficient mice (Lman1gt1/gt1) was confirmed in Lman1−/− mice, although it was not observed in Lman1cgt/cgt mice. Taken together, these results show a dose-dependent effect of residual LMAN1 on the secretion of its cargo proteins. The results also suggest that human subjects with hypomorphic LMAN1 mutations might present with mild bleeding phenotypes resulting from more modest reductions in FV and FVIII, which could be missed by routine clinical evaluation. Finally, these findings suggest that therapeutic targeting of LMAN1 to reduce FV and FVIII as an anticoagulant strategy may only require partial inhibition of LMAN1 function.

scholarly journals Reconstructing a wild-type Pseudomonas aeruginosa reference strain PAO1

2021 ◽  
Author(s):  
Samuel Lee ◽  
Larry Gallagher ◽  
Colin Manoil
Keyword(s):  
Reference Strain ◽  
Genetic Selection ◽  
Loss Of Function ◽  
Wild Type ◽  
Regulatory Mutation ◽  
Phenotypic Analysis ◽  
Strain Pao1 ◽  
Suppressor Mutations ◽  
Wild Type Parent ◽  
Selection Of

The P. aeruginosa reference strain PAO1 has been used to delineate much of the physiology, metabolism and fundamental biology of the species. The wild-type parent of PAO1 was lost, and PAO1 carries a regulatory mutation introduced for positive genetic selection that affects antibiotic resistance, virulence, quorum sensing and other traits. The mutation is a loss-of-function change in an oxidoreductase gene (mexS), which constitutively activates a stress response controlled by a positive regulator (MexT). Fitness defects associated with the constitutive response have led to the inadvertent selection of mexT– suppressor mutations, creating genetic heterogeneity in PAO1 sublines studied in different laboratories. To help circumvent complications due to the mexS–minus phenotypes, we created a wild-type version of PAO1 (called LPAO) by “reverting” its mexS to the functional allele likely to have been in its parent. Phenotypic analysis revealed that the mexS– allele in PAO1 makes growth sensitive to salt (NaCl) and is lethal when combined with mutations inactivating the major sodium antiporter (ShaABCDEF). The salt sensitivity of PAO1 may underlie some complex mexS– phenotypes and help explain the selection of mexT– suppressor mutations. To facilitate genetic comparisons of PAO1, LPAO and other P. aeruginosa strains, we developed a transformation procedure to transfer selectable alleles, such as transposon insertion alleles, between strains. Overall, the study helps explain phenotypic heterogeneity of PAO1-derived strains and provides resources to help recognize and eliminate difficulties due to it. IMPORTANCE The P. aeruginosa reference strain PAO1 carries a regulatory mutation that may affect processes characterized in it. To eliminate complications due to the mutation, we constructed a version of the missing wild-type parent strain and developed methods to transfer mutations between PAO1 and the new strain. The methods are likely to be applicable to other isolates of P. aeruginosa as well.

scholarly journals Arabidopsis V-ATPase d2 subunit plays a role in plant responses to oxidative stress

2020 ◽  
Author(s):  
Shuang Feng ◽  
Yun Peng ◽  
Enhui Liu ◽  
Hongping Ma ◽  
Kun Qiao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Developmental Stages ◽  
Plant Responses ◽  
Rna Seq ◽  
Wild Type ◽  
Phenotypic Analysis ◽  
Non Invasive ◽  
Atpase Gene ◽  
D Subunit ◽  
And Oxidative Stress

Abstract Background: Vacuolar-type H + -ATPase (V-ATPase) is a multisubunit proton pump located on the endomembranes, which plays an important role in plant growth. The Arabidopsis V-ATPase d subunit consists of two isoforms, AtVHA-d1 and AtVHA-d2. Results: In this study, the function of the AtVHA-d2 gene was investigated. Histochemical analysis revealed that the AtVHA-d1 and AtVHA-d2 genes were generally and highly overlapping expressed in multiple tissues at different developmental stages of Arabidopsis. Subcellular localization showed that AtVHA-d2 was mainly localized to the vacuole. The AtVHA-d2 expression was significantly induced by oxidative stress. Furthermore, the phenotypic analysis showed that the atvha-d2 mutant was sensitive to oxidative stress. The non-invasive micro-test measurement demonstrated that the net H + influx in the atvha-d2 roots was weaker than that of the wild type under normal conditions. However, oxidative stress resulted in the H + efflux in atvha-d2 roots, which was significantly different from the wild type. RNA-seq combined with qPCR analysis showed that the expression of several members of the plasma membrane H + -ATPase gene ( AtAHA ) family in atvha-d2 were significant different from wild type under normal and oxidative stress. Conclusion: Overall, our results indicate that AtVHA-d2 plays a role in Arabidopsis in response to oxidative stress by affecting H + flux and AtAHA gene expression.

scholarly journals Hypertension induces glomerulosclerosis in phospholipase C-ε1 deficiency

2020 ◽  
Vol 318 (5) ◽  
pp. F1177-F1187 ◽  
Author(s):  
Douglas K. Atchison ◽  
Christopher L. O’Connor ◽  
Rajasree Menon ◽  
Edgar A. Otto ◽  
Santhi K. Ganesh ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Phospholipase C ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Ang Ii ◽  
Loss Of Function ◽  
Wild Type ◽  
Podocyte Loss ◽  
Deficient Mice ◽  
Glomerular Damage

Loss-of-function mutations in phospholipase C-ε1 (PLCE1) have been detected in patients with nephrotic syndrome, but other family members with the same mutation were asymptomatic, suggesting additional stressor are required to cause the full phenotype. Consistent with these observations, we determined that global Plce1-deficient mice have histologically normal glomeruli and no albuminuria at baseline. Angiotensin II (ANG II) is known to induce glomerular damage in genetically susceptible individuals. Therefore, we tested whether ANG II enhances glomerular damage in Plce1-deficient mice. ANG II increased blood pressure equally in Plce1-deficient and wild-type littermates. Additionally, it led to 20-fold increased albuminuria and significantly more sclerotic glomeruli in Plce1-deficient mice compared with wild-type littermates. Furthermore, Plce1-deficient mice demonstrated diffuse mesangial expansion, podocyte loss, and focal podocyte foot process effacement. To determine whether these effects are mediated by hypertension and hyperfiltration, rather than directly through ANG II, we raised blood pressure to a similar level using DOCA + salt + uninephrectomy and norepinephrine. This caused a fivefold increase in albuminuria in Plce1-deficient mice and a significant increase in the number of sclerotic glomeruli. Consistent with previous findings in mice, we detected strong PLCE1 transcript expression in podocytes using single cell sequencing of human kidney tissue. In hemagglutinin-tagged Plce1 transgenic mice, Plce1 was detected in podocytes and also in glomerular arterioles using immunohistochemistry. Our data demonstrate that Plce1 deficiency in mice predisposes to glomerular damage secondary to hypertensive insults.

Smc3 Haploinsufficiency and Smc3 Deletion Alter Hematopoiesis In Vivo

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2903-2903
Author(s):  
Tianjiao Wang ◽  
John S. Welch
Keyword(s):  
Bone Marrow ◽  
Complete Loss ◽  
Dominant Negative ◽  
Loss Of Function ◽  
Wild Type ◽  
Embryonic Lethal ◽  
The Impact ◽  
Deficient Mice

Abstract Recurrent mutations in SMC3, encoding a cohesin subunit, have been identified in acute myeloid leukemia (AML) and other myeloid malignancies by our group and others. SMC3 mutations are heterozygous in AML patients. Missense, nonsense, and splice site mutations have been observed across all domains of SMC3. Given the breath of mutations, it is important to determine whether these represent recurrent loss-of-function mechanisms, or if some might have dominant negative effects. To determine the impact of Smc3 deletion on hematopoiesis, we studied both Smc3 haploinsufficient and Smc3 deficient mice as models of loss-of function and dominant negative phenotypes respectively. The Smc3 haploinsufficient mouse model has a lacZneo gene trap inserted in intron 3-4 of Smc3, which leads to a premature transcription stop and therefore produces a truncated and dysfunctional protein. The homozygous Smc3trap allele is embryonic lethal. The Smc3trap/+mice have an early growth defect, although their body weight catches up to wild type mice after 6 weeks of age. We found no difference in spleen weights, peripheral blood counts, and bone marrow (BM) compositions between Smc3trap/+ and wild type mice. The Smc3trap/+ BM cells formed similar number of colonies as wild type cells when plated in methylcellulose in vitro and lost self-renewal capabilities after replating for two weeks. Competitive repopulation assay in vivo showed neither advantage nor disadvantage for the Smc3trap/+BM cells (n=10). Thus, Smc3trap/+BM cells have normal colony forming capacity in vitro and normal homeostatic feedback in vivo. Further, we generated Smc3 conditionally deficient mice by removing the gene-trap cassette, which retains the loxP sites flanking exon 4 (Smc3fl), and crossing these mice with either Vav1-Cre+/- or ERT2-Cre+/- to delete the allele (Smc3fl/+/Vav1-Cre+/- is constitutively haploinsufficient in hematopoietic cells, whereas Smc3fl/+/ERT2-Cre+/-is only haploinsufficient when induced with tamoxifen). We characterized both models by serial replating assays, flow cytometry assays for hematopoietic stem/progenitor cells (HSPCs), and BM lineage in vitro and found no difference in these mice compared to the Smc3fl/+control. In contrast to the Smc3fl/+/Mx1-Cre+/- mice (Viny et al. JEM 212 (11): 1819-1832), we observed a significant competitive disadvantage for the Smc3fl/+/ERT2-Cre+/-BM cells (p<0.0001, n=10), most pronounced in Gr1+ myeloid cells in vivo (p<0.0001), implying Smc3 haploinsufficiency alters hematopoiesis in those mice in vivo. We characterized the effects of homozygous Smc3 loss on hematopoiesis in the inducible Smc3fl/fl/ERT2-Cre+/- mice by treating mice with tamoxifen at 6 weeks of age (Smc3fl/fl/Vav1-Cre+/- is embryonic lethal). Deletion of Smc3 led to rapid bone marrow failure and 100% lethality with a median survival of 8 days (n=4, 2 independent experiments). At the time of death, we observed severe reduction in the sizes of spleen (Sp) and thymus (Thy), in total number of BM, Sp, and Thy cells, and in white blood counts, lymphocytes, monocytes, and platelets. The Smc3 deficient BM cells had decreased levels of Smc3 by Western blot. The impact of Smc3 deletion on HSPC functions in vivo was assessed by a competitive repopulation assay of Smc3fl/fl/ERT2-Cre+/-BM cells (p<0.0001, n=10). Recipient mice were treated with tamoxifen after 6-week engraftment. After tamoxifen-mediated deletion, Smc3 deficient cells were rapidly outcompeted in vivo, indicating complete loss of HSPC functions. Collectively, these results suggest that Smc3 is necessary for normal hematopoiesis and for HSPC functions. The AML-associated SMC3 mutations are therefore unlikely to be dominant negative because the complete loss of Smc3 is incompatible with hematopoiesis. Disclosures No relevant conflicts of interest to declare.

Different effects of chronic helicobactor pylori infection on parietal and ECL cells between wild type and gastrin-deficient mice

2001 ◽  
Vol 120 (5) ◽  
pp. A728-A728
Author(s):  
D CHEN ◽  
L FRIISHANSEN ◽  
X WANG ◽  
C ZHAO ◽  
H WALDUM ◽  
...  
Keyword(s):  
Wild Type ◽  
Ecl Cells ◽  
Helicobactor Pylori ◽  
Deficient Mice
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