INZ ‐701 prevents ectopic tissue calcification and restores bone architecture and growth in ENPP1 deficient mice

2021 ◽  
Author(s):  
Zhiliang Cheng ◽  
Kevin O'Brien ◽  
Jennifer Howe ◽  
Caitlin Sullivan ◽  
Denis Schrier ◽  
...  
Keyword(s):  
Bone Architecture ◽  
Tissue Calcification ◽  
Ectopic Tissue ◽  
Deficient Mice

scholarly journals Partial Reversal of Tissue Calcification and Extension of Life Span following Ammonium Nitrate Treatment of Klotho-Deficient Mice

2016 ◽  
Vol 41 (1) ◽  
pp. 99-107 ◽  
Author(s):  
Christina B. Leibrock ◽  
Martina Feger ◽  
Jakob Voelkl ◽  
Ursula Kohlhofer ◽  
Leticia Quintanilla-Martinez ◽  
...  
Keyword(s):  
Life Span ◽  
Ammonium Nitrate ◽  
Tissue Calcification ◽  
Nitrate Treatment ◽  
Deficient Mice ◽  
Partial Reversal

scholarly journals Microvasculopathy And Soft Tissue Calcification In Mice Are Governed by Fetuin-A, Pyrophosphate And Magnesium

2019 ◽  
Author(s):  
Anne Babler ◽  
Carlo Schmitz ◽  
Andrea Büscher ◽  
Marietta Herrmann ◽  
Felix Gremse ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Molecular Genetic ◽  
Extracellular Fluid ◽  
Molecular Genetic Analysis ◽  
Ectopic Calcification ◽  
Special Importance ◽  
Soft Tissue Calcification ◽  
Fetuin A ◽  
Tissue Calcification ◽  
Deficient Mice

AbstractObjectiveCalcifications can disrupt organ function in the cardiovascular system and the kidney, and are particularly common in patients with chronic kidney disease (CKD). Fetuin-A deficient mice maintained against the genetic background DBA/2 exhibit particularly severe soft tissue calcifications, while fetuin-A deficient C57BL/6 mice remain healthy. We employed molecular genetic analysis to identify risk factors of calcification in fetuin-A deficient mice. We sought to identify pharmaceutical therapeutic target that could be influenced by dietary of parenteral supplementation.Approach and ResultsWe studied the progeny of an intercross of fetuin-A deficient DBA/2 and C57BL/6 mice to identify candidate risk genes involved in calcification. We determined that a hypomorphic mutation of the Abcc6 gene, a liver ATP transporter supplying systemic pyrophosphate, and failure to regulate the TRPM6 magnesium transporter in kidney were associated with severity of calcification. Calcification prone fetuin-A deficient mice were alternatively treated with dietary phosphate restriction, magnesium supplementation, or by parenteral administration of fetuin-A or pyrophosphate. All treatments markedly reduced soft tissue calcification, demonstrated by computed tomography, histology and tissue calcium measurement.ConclusionsWe show that pathological ectopic calcification in fetuin-A deficient DBA/2 mice is caused by a compound deficiency of three major extracellular and systemic inhibitors of calcification, namely fetuin-A, pyrophosphate, and magnesium. All three of these are individually known to contribute to stabilize protein-mineral complexes and thus inhibit mineral precipitation from extracellular fluid. We show for the first time a compound triple deficiency that can be treated by simple dietary or parenteral supplementation. This is of special importance in patients with advanced CKD, who commonly exhibit reduced serum fetuin-A, pyrophosphate and magnesium levels.Subject CodesAnimal Models of Human Disease, Fibrosis, Inflammation, Proteomics, Peripheral Vascular Disease

Bicarbonate-sensitive calcification and lifespan of klotho-deficient mice

2016 ◽  
Vol 310 (1) ◽  
pp. F102-F108 ◽  
Author(s):  
Christina B. Leibrock ◽  
Jakob Voelkl ◽  
Ursula Kohlhofer ◽  
Leticia Quintanilla-Martinez ◽  
Makoto Kuro-o ◽  
...  
Keyword(s):  
Vascular Calcification ◽  
Mineral Metabolism ◽  
Plasma Concentrations ◽  
Extracellular Volume ◽  
Early Death ◽  
Volume Depletion ◽  
Deficient Diet ◽  
Plasma Aldosterone Concentration ◽  
Tissue Calcification ◽  
Deficient Mice

Klotho, a protein counteracting aging, is a powerful inhibitor of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] formation and regulator of mineral metabolism. In klotho hypomorphic ( kl/kl) mice, excessive 1,25(OH)2D3 formation leads to hypercalcemia, hyperphosphatemia and vascular calcification, severe growth deficits, accelerated aging and early death. Kl/kl mice further suffer from extracellular volume depletion and hypotension, leading to the stimulation of antidiuretic hormone and aldosterone release. A vitamin D-deficient diet, restriction of dietary phosphate, inhibition of mineralocorticoid receptors with spironolactone, and dietary NaCl all extend the lifespan of kl/kl mice. Kl/kl mice suffer from acidosis. The present study explored whether replacement of tap drinking water by 150 mM NaHCO3 affects the growth, tissue calcification, and lifespan of kl/kl mice. As a result, NaHCO3 administration to kl/kl mice did not reverse the growth deficit but substantially decreased tissue calcification and significantly increased the average lifespan from 78 to 127 days. NaHCO3 did not significantly affect plasma concentrations of 1,25(OH)2D3 and Ca2+ but significantly decreased plasma phosphate concentration and plasma aldosterone concentration. The present study reveals a novel effect of bicarbonate, i.e., a favorable influence on vascular calcification and early death of klotho-deficient mice.

Comparison of localization of metallothionein in tissues of metallothionein-deficient mice

1995 ◽  
Vol 53 ◽  
pp. 1042-1043
Author(s):  
H. Nishimura ◽  
R Nishimura ◽  
D.L. Adelson ◽  
A.E. Michaelska ◽  
K.H.A. Choo ◽  
...  
Keyword(s):  
Metal Binding ◽  
Immunohistochemical Staining ◽  
Squamous Epithelium ◽  
Rabbit Antiserum ◽  
Slight Modification ◽  
Positive Control ◽  
Heavy Metal Binding ◽  
Critical Organ ◽  
Metal Binding Protein ◽  
Deficient Mice

Metallothionein (MT), a cysteine-rich heavy metal binding protein, has several isoforms designated from I to IV. Its major isoforms, I and II, can be induced by heavy metals like cadmium (Cd) and, are present in various organs of man and animals. Rodent testes are a critical organ to Cd and it is still a controversial matter whether MT exists in the testis although it is clear that MT is not induced by Cd in this tissue. MT-IV mRNA was found to localize within tongue squamous epithelium. Whether MT-III is present mainly glial cells or neurons has become a debatable topic. In the present study, we have utilized MT-I and II gene targeted mice and compared MT localization in various tissues from both MT-deficient mice and C57Black/6J mice (C57BL) which were used as an MT-positive control. For MT immunostaining, we have used rabbit antiserum against rat MT-I known to cross-react with mammalian MT-I and II and human MT-III. Immunohistochemical staining was conducted by the method described in the previous paper with a slight modification after the tissues were fixed in HistoChoice and embedded in paraffin.

Early ossicle growth in the regenerating disc of a brittle star

1994 ◽  
Vol 52 ◽  
pp. 364-365
Author(s):  
M. Shlepr ◽  
R. L. Turner
Keyword(s):  
Cell Membrane ◽  
Light Microscopy ◽  
De Novo ◽  
Current Model ◽  
Syncytium Formation ◽  
Brittle Star ◽  
Intracellular Location ◽  
Limited Volume ◽  
Tissue Calcification

Calcification in the echinoderms occurs within a limited-volume cavity enclosed by cytoplasmic extensions of the mineral depositing cells, the sclerocytes. The current model of this process maintains that the sheath formed from these cytoplasmic extensions is syncytial. Prior studies indicate that syncytium formation might be dependent on sclerocyte density and not required for calcification. This model further envisions that ossicles formed de novo nucleate and grow intracellularly until the ossicle effectively outgrows the vacuole. Continued ossicle growth occurs within the sheath but external to the cell membrane. The initial intracellular location has been confirmed only for elements of the echinoid tooth.The regenerating aboral disc integument of ophiophragmus filograneus was used to test the current echinoderm calcification model. This tissue is free of calcite fragments, thus avoiding questions of cellular engulfment, and ossicles are formed de novo. The tissue calcification pattern was followed by light microscopy in both living and fixed preparations.

Alterations during Positive Selection in the Thymus of nackt CD4-Deficient Mice

2000 ◽  
Vol 52 (6) ◽  
pp. 555-562 ◽  
Author(s):  
I. Nepomnaschy ◽  
G. Lombardi ◽  
P. Bekinschtein ◽  
P. Berguer ◽  
V. Francisco ◽  
...  
Keyword(s):  
Positive Selection ◽  
Deficient Mice

Gubernacular development in Müllerian inhibiting substance receptor-deficient mice

2002 ◽  
Vol 89 (1) ◽  
pp. 113-118 ◽  
Author(s):  
J.E. Bartlett ◽  
S.M.Y. Lee ◽  
Y. Mishina ◽  
R.R. Behringer ◽  
N. Yang ◽  
...  
Keyword(s):  
Müllerian Inhibiting Substance ◽  
Deficient Mice ◽  
Mullerian Inhibiting Substance

Characterization of Helicobacter-induced inflammatory bowel disease in IL-10 -/- and T cell deficient mice

2001 ◽  
Vol 120 (5) ◽  
pp. A523-A523
Author(s):  
A BURICH ◽  
R HERSHBERG ◽  
K WAGGIE ◽  
W ZENG ◽  
J VINEY ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
T Cell ◽  
Bowel Disease ◽  
Inflammatory Bowel ◽  
Deficient Mice
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