scholarly journals APOL1 is not expressed in proximal tubules and is not filtered

2019 ◽  
Author(s):  
Natalya A. Blessing ◽  
Zhenzhen Wu ◽  
Sethu Madhavan ◽  
Myung K. Shin ◽  
Maarten Hoek ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Bacterial Artificial Chromosome ◽  
Transgenic Mice ◽  
Proximal Tubule ◽  
Expression Pattern ◽  
Artificial Chromosome ◽  
Proximal Tubules ◽  
Mechanistic Studies

AbstractThe kidney expression pattern of APOL1 was examined using both protein and mRNAin situmethods onAPOL1bacterial artificial chromosome transgenic mice, with and without proteinuria. APOL1 was detected in podocytes and endothelial cells of the kidney, but was not expressed in tubular epithelia, nor was plasma APOL1 protein filtered and reabsorbed by the proximal tubule. APOL1 expression in podocytes and endothelia should remain the focus for mechanistic studies of APOL1-mediated pathogenesis.

scholarly journals Lack of APOL1 in proximal tubules of normal human kidneys and proteinuric APOL1 transgenic mouse kidneys

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0253197
Author(s):  
Natalya A. Blessing ◽  
Zhenzhen Wu ◽  
Sethu M. Madhavan ◽  
Jonathan W. Choy ◽  
Michelle Chen ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Kidney Diseases ◽  
Expression Patterns ◽  
Artificial Chromosome ◽  
Proximal Tubules ◽  
Kidney Cells ◽  
Renal Cells ◽  
Normal Human ◽  
Commercial Antibodies

The mechanism of pathogenesis associated with APOL1 polymorphisms and risk for non-diabetic chronic kidney disease (CKD) is not fully understood. Prior studies have minimized a causal role for the circulating APOL1 protein, thus efforts to understand kidney pathogenesis have focused on APOL1 expressed in renal cells. Of the kidney cells reported to express APOL1, the proximal tubule expression patterns are inconsistent in published reports, and whether APOL1 is synthesized by the proximal tubule or possibly APOL1 protein in the blood is filtered and reabsorbed by the proximal tubule remains unclear. Using both protein and mRNA in situ methods, the kidney expression pattern of APOL1 was examined in normal human and APOL1 bacterial artificial chromosome transgenic mice with and without proteinuria. APOL1 protein and mRNA was detected in podocytes and endothelial cells, but not in tubular epithelia. In the setting of proteinuria, plasma APOL1 protein did not appear to be filtered or reabsorbed by the proximal tubule. A side-by-side examination of commercial antibodies used in prior studies suggest the original reports of APOL1 in proximal tubules likely reflects antibody non-specificity. As such, APOL1 expression in podocytes and endothelia should remain the focus for mechanistic studies in the APOL1-mediated kidney diseases.

Expression pattern of the V5‐Ostm1 protein in bacterial artificial chromosome transgenic mice

genesis ◽  
2021 ◽  
Author(s):  
Monica Pata ◽  
Pardis Yousefi Behzadi ◽  
Jean Vacher
Keyword(s):  
Bacterial Artificial Chromosome ◽  
Transgenic Mice ◽  
Expression Pattern ◽  
Artificial Chromosome

The murine platelet and plasma factor V pools are biosynthetically distinct and sufficient for minimal hemostasis

Blood ◽  
2003 ◽  
Vol 102 (8) ◽  
pp. 2856-2861 ◽  
Author(s):  
Hongmin Sun ◽  
Tony L. Yang ◽  
Angela Yang ◽  
Xixi Wang ◽  
David Ginsburg
Keyword(s):  
Gene Expression ◽  
Bacterial Artificial Chromosome ◽  
Transgenic Mice ◽  
Coagulation Factor ◽  
Artificial Chromosome ◽  
Coagulation Cascade ◽  
Factor V ◽  
Wild Type ◽  
Plasma Factor ◽  
Coagulation Factor V

Abstract Coagulation factor V (FV) is a central regulator of the coagulation cascade. Circulating FV is found in plasma and within platelet α granules. The specific functions of these distinct FV pools are uncertain. We now report the generation of transgenic mice with FV gene expression restricted to either the liver or megakaryocyte/platelet lineage using bacterial artificial chromosome (BAC) constructs. Six of 6 independent albumin BAC transgenes rescue the neonatal lethal hemorrhage of FV deficiency. Rescued mice all exhibit liver-specific Fv expression at levels ranging from 6% to 46% of the endogenous Fv gene, with no detectable FV activity within the platelet pool. One of the 3 Pf4 BAC transgenes available for analysis also rescues the lethal FV null phenotype, with FV activity restricted to only the platelet pool (approximately 3% of the wild-type FV level). FV-null mice rescued by either the albumin or Pf4 BAC exhibit nearly normal tail bleeding times. These results demonstrate that Fv expression in either the platelet or plasma FV pool is sufficient for basal hemostasis. In addition, these findings indicate that the murine platelet and plasma FV pools are biosynthetically distinct, in contrast to a previous report demonstrating a plasma origin for platelet FV in humans.

scholarly journals Characterization of bacterial artificial chromosome transgenic mice expressing mCherry fluorescent protein substituted for the murine smooth muscle α-actin gene

genesis ◽  
2010 ◽  
Vol 48 (7) ◽  
pp. 457-463 ◽  
Author(s):  
John J. Armstrong ◽  
Irina V. Larina ◽  
Mary E. Dickinson ◽  
Warren E. Zimmer ◽  
Karen K. Hirschi
Keyword(s):  
Smooth Muscle ◽  
Bacterial Artificial Chromosome ◽  
Transgenic Mice ◽  
Fluorescent Protein ◽  
Artificial Chromosome ◽  
Actin Gene

Improved Pituitary Specificity of Cre Recombinase Transgenic Mice by Recombineering of a Mouse αGSU Bacterial Artificial Chromosome

2011 ◽  
pp. P1-383-P1-383
Author(s):  
Maria Ines Perez Millan ◽  
Sally A Camper ◽  
Shannon W Davis
Keyword(s):  
Bacterial Artificial Chromosome ◽  
Transgenic Mice ◽  
Artificial Chromosome ◽  
Cre Recombinase

Horizontal Transfer of DNA by the Uptake of Apoptotic Bodies

Blood ◽  
1999 ◽  
Vol 93 (11) ◽  
pp. 3956-3963 ◽  
Author(s):  
Lars Holmgren ◽  
Anna Szeles ◽  
Eva Rajnavölgyi ◽  
Judah Folkman ◽  
Georg Klein ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
In Situ Hybridization ◽  
Expression Pattern ◽  
Cell Lines ◽  
Immunofluorescent Staining ◽  
Apoptotic Bodies ◽  
Aortic Endothelial Cells ◽  
Bovine Aortic Endothelial Cells ◽  
Aortic Endothelial

In this study we have raised the question of whether DNA can be transferred from one cell to another by phagocytosis of apoptotic bodies. We have used integrated copies of the Epstein-Barr virus (EBV) as a marker to follow the fate and expression pattern of apoptotic DNA in the phagocytotic host. Apoptosis was induced in EBV-carrying cell lines by irradiation before cultivation with either human fibroblasts, macrophages, or bovine aortic endothelial cells. Analysis of the expression pattern of EBV-encoded genes was performed by immunofluorescent staining as well as in situ hybridization. Cocultivation of apoptotic bodies from lymphoid cell lines containing integrated but not episomal copies of EBV resulted in expression of the EBV-encoded genes EBER and EBNA1 in the recipient cells at a high frequency. Fluorescence in situ hybridization analysis showed uptake of human chromatin as well as integrated EBV-DNA into the nuclei of bovine aortic endothelial cells. These data show that DNA may be rescued and reused from apoptotic bodies by somatic cells. In addition, our findings suggest that apoptotic bodies derived from EBV-carrying B lymphocytes may serve as the source of viral transfer to cells that lack receptors for the EBV virus in vivo.

Corrigendum to “Distribution of estrogen receptor beta containing cells in the brains of bacterial artificial chromosome transgenic mice” [Brain Res. 1351 (2010) 74–96]

2011 ◽  
Vol 1396 ◽  
pp. 105
Author(s):  
Teresa A. Milner ◽  
Louisa I. Thompson ◽  
Gang Wang ◽  
Justin A. Kievits ◽  
Eugene Martin ◽  
...  
Keyword(s):  
Estrogen Receptor ◽  
Bacterial Artificial Chromosome ◽  
Transgenic Mice ◽  
Estrogen Receptor Beta ◽  
Artificial Chromosome ◽  
Mice Brain ◽  
Receptor Beta

Effects of formate and oxalate on volume absorption in rat proximal tubule

1992 ◽  
Vol 263 (1) ◽  
pp. F37-F42 ◽  
Author(s):  
T. Wang ◽  
G. Giebisch ◽  
P. S. Aronson
Keyword(s):  
Proximal Tubule ◽  
Channel Blocker ◽  
Ringer Solution ◽  
Proximal Tubules ◽  
Solution Ph ◽  
Physiological Range ◽  
Volume Absorption ◽  
Peritubular Capillaries ◽  
Rat Proximal Tubule

We examined the effects of formate and oxalate on the rate of fluid absorption (Jv) in the rat proximal convoluted tubule in situ. Proximal tubules were microperfused with a high-Cl-, low-HCO3- Ringer solution (pH 6.7), and the peritubular capillaries were perfused with a standard Ringer solution (pH 7.4), simulating conditions in the late proximal tubule. Jv, a measure of transtubular NaCl absorption under these conditions, was calculated from the change in luminal [3H]inulin. Addition of formate in the physiological range (500 microM) to the luminal perfusate increased Jv by 45%; addition of 500 microM formate to both luminal and capillary perfusates increased Jv by 57%. Similarly, addition of oxalate in the physiological range (5 microM) to the luminal perfusate increased Jv by 37%; addition of 5 microM oxalate to both luminal and capillary perfusates increased Jv by 57%. The stimulatory effects of formate and oxalate perfused in the lumen and capillaries were not additive. Addition of 4,4'-diisothiocyanostilbene-2,2'-disulfonate (DIDS, 0.1 mM) to the luminal perfusate had no effect on baseline Jv measured in the absence of added formate and oxalate but completely abolished the increment in Jv induced by formate and oxalate. Addition of the Cl(-)-channel blocker diphenylamine-2-carboxylate (DPC, 0.2 mM) to the capillary perfusate had no effect on baseline Jv but completely abolished the increment in Jv induced by formate and oxalate.(ABSTRACT TRUNCATED AT 250 WORDS)

Single proximal tubules of Necturus kidney. VIII: Na and K determinations by glass electrodes

1963 ◽  
Vol 204 (5) ◽  
pp. 743-748 ◽  
Author(s):  
Raja N. Khuri ◽  
David A. Goldstein ◽  
David L. Maude ◽  
Charles Edmonds ◽  
A. K. Solomon
Keyword(s):  
Proximal Tubule ◽  
Distal Portion ◽  
Proximal Tubules ◽  
Living Animal ◽  
Flame Photometer ◽  
Proximal Tubular ◽  
Glass Electrodes ◽  
K Concentration

Cation-sensitive glass electrodes have been used to measure Na and K concentrations in Necturus serum and in glomerular and proximal tubular fluid from Necturus kidney. It has been found that the ratio [Na]glomerulus/[Na]serum is 1.00 ± 0.02 and the ratio [Na]tubule/[Na]glomerulus is 0.99 ± 0.01 thus confirming previous measurements with the flame photometer which indicated that tubular Na concentration did not change as fluid moved along the proximal tubule in Necturus kidney. These results were also confirmed with cation electrodes placed in situ in the living animal. The K concentration in fluid collected from the most distal portion of the proximal tubule was found to be 1.8 ± 0.1 times more concentrated than that in the glomerulus, in agreement with a ratio of 1.6 ± 0.1 previously obtained on the basis of flame photometer measurements by Oken and Solomon.

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