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Articles 1 - 30 of 47
Full-Text Articles in Cell and Developmental Biology
Shar-Pei Mediates Cell Proliferation Arrest During Imaginal Disc Growth In Drosophila, Madhuri Kango-Singh, Riitta Nolo, Chunyao Tao, Patrik Verstreken, P. Robin Hiesinger, Hugo J. Bellen, Georg Halder
Shar-Pei Mediates Cell Proliferation Arrest During Imaginal Disc Growth In Drosophila, Madhuri Kango-Singh, Riitta Nolo, Chunyao Tao, Patrik Verstreken, P. Robin Hiesinger, Hugo J. Bellen, Georg Halder
Biology Faculty Publications
During animal development, organ size is determined primarily by the amount of cell proliferation, which must be tightly regulated to ensure the generation of properly proportioned organs. However, little is known about the molecular pathways that direct cells to stop proliferating when an organ has attained its proper size. We have identified mutations in a novel gene, shar-pei, that is required for proper termination of cell proliferation during Drosophila imaginal disc development. Clones of shar-pei mutant cells in imaginal discs produce enlarged tissues containing more cells of normal size. We show that this phenotype is the result of both …
Historical Development Of The Linear Nonthreshold Dose-Response Model As Applied To Radiation, Ronald L. Kathren
Historical Development Of The Linear Nonthreshold Dose-Response Model As Applied To Radiation, Ronald L. Kathren
The University of New Hampshire Law Review
[Excerpt] "Despite the nearly universal adoption of the linear nonthreshold dose response model (LNT) as the primary basis for radiation protection standards for the past half century, the LNT remains highly controversial and a contentious topic of discussion among health physicists, radiation biologists, and other radiological scientists. Indeed, it has been pointed out that the LNT has assumed the status of a paradigm, synonymous with an ideal, standard, or paragon or perhaps to some, a sacred cow. Reduced to its very basics, the LNT postulates that every increment of ionizing radiation dose, however small, carries with it a commensurate increase …
Anisomycin Activates Jnk And Sensitises Du 145 Prostate Carcinoma Cells To Fas Mediated Apoptosis, James Curtin, Thomas Cotter
Anisomycin Activates Jnk And Sensitises Du 145 Prostate Carcinoma Cells To Fas Mediated Apoptosis, James Curtin, Thomas Cotter
Articles
Treatment of the hormone refractory prostate cancer cell line DU 145 with sublethal concentrations of chemotherapeutic drugs has been reported to sensitise these cells to Fas mediated apoptosis. However, the mechanism by which this occurs has not been determined. Our group has shown that inhibition of JNK activity completely abrogates the effects of chemotherapeutic drugs. Using anisomycin, a potent JNK agonist, we have demonstrated a role for JNK in Fas mediated apoptosis in DU 145 cells. Inhibition of Caspase 8 and Caspase 9 completely inhibits this process which suggests that DU 145 cells require mitochondrial amplification of the Fas apoptotic …
Endocytic Intermediates Involved With The Intracellular Trafficking Of A Fluorescent Cellular Prion Protein, Ac Magalhaes, Ja Silva, Vr Martins, Vf Prado, Ssg Ferguson, Mv Gomez, Rr Brentani, Mam Prado
Endocytic Intermediates Involved With The Intracellular Trafficking Of A Fluorescent Cellular Prion Protein, Ac Magalhaes, Ja Silva, Vr Martins, Vf Prado, Ssg Ferguson, Mv Gomez, Rr Brentani, Mam Prado
Anatomy and Cell Biology Publications
We have investigated the intracellular traffic of PrPc, a glycosylphosphatidylinositol (GPI)-anchored protein implicated in spongiform encephalopathies. A fluorescent functional green fluorescent protein (GFP)-tagged version of PrPc is found at the cell surface and in intracellular compartments in SN56 cells. Confocal microscopy and organelle-specific markers suggest that the protein is found in both the Golgi and the recycling endosomal compartment. Perturbation of endocytosis with a dynamin I-K44A dominant-negative mutant altered the steady-state distribution of the GFP-PrPc, leading to the accumulation of fluorescence in unfissioned endocytic intermediates. These pre-endocytic intermediates did not seem to accumulate GFP-GPI, a minimum GPI-anchored protein, suggesting that …
The Tadpole Of Proceratophrys Avelinoi (Anura: Leptodactylidae), Rafael O. De Sá, José A. Langone
The Tadpole Of Proceratophrys Avelinoi (Anura: Leptodactylidae), Rafael O. De Sá, José A. Langone
Biology Faculty Publications
The genus Proceratoprhys is poorly known. It consists of 14 currently recognized species (Frost, 2000) of medium-sized frogs distributed from northeastern Argentina and Paraguay to southeast Amazonia (Rondonia State), eastern and southern Brazil Proceratophrys avelinoi was described from Misiones, Argentina (Mercadal de Barrio and Barrio, 1993). The larval stage of this species is unknown. Herein, we describe the tadpole and the characteristics of the internal oral anatomy of P. avelinoi using scanning electron microscopy (SEM).
Eye Suppression, A Novel Function Of Teashirt, Requires Wingless Signaling, Amit Singh, Madhuri Kango-Singh, Y. Henry Sun
Eye Suppression, A Novel Function Of Teashirt, Requires Wingless Signaling, Amit Singh, Madhuri Kango-Singh, Y. Henry Sun
Biology Faculty Publications
Teashirt (tsh) encodes a Drosophila zinc-finger protein. Misexpression of tsh has been shown to induce ectopic eye formation in the antenna. We report that tsh can suppress eye development. This novel function of tsh is due to the induction of homothorax (hth), a known repressor of eye development, and requires Wingless (WG) signaling. Interestingly, tsh has different functions in the dorsal and ventral eye, suppressing eye development close to the ventral margin, while promoting eye development near the dorsal margin. It affects both growth of eye disc and retinal cell differentiation.
The Tadpole Of Proceratophrys Avelinoi (Anura: Leptodactylidae), Rafael O. De Sá, José A. Langone
The Tadpole Of Proceratophrys Avelinoi (Anura: Leptodactylidae), Rafael O. De Sá, José A. Langone
Biology Faculty Publications
The genus Proceratoprhrys is poorly known. It consists of 14 currently recognized species (Frost, 2000) of medium-sized frogs distributed from northeastern Argentina and Paraguay to southeast Amazonia (Rondonia State), eastern and southern Brazil. Proceratophrys avelinoi was described from Misiones, Argentina (Mercadal de Barrio and Barrio, 1993). The larval stage of this species is unknown. Herein, we describe the tadpole and the characteristics of the internal oral anatomy of P avelinoi using scanning electron micros- copy (SEM).
Within-Litter Birth Weight Variation In The Domestic Pig And Its Relation To Pre-Weaning Survival, Weight Gain, And Variation In Weaning Weights, Barry N. Milligan, David Fraser, Donald L. Kramer
Within-Litter Birth Weight Variation In The Domestic Pig And Its Relation To Pre-Weaning Survival, Weight Gain, And Variation In Weaning Weights, Barry N. Milligan, David Fraser, Donald L. Kramer
Ontogeny Collection
To determine the relationship between within-litter birth weight variation and pre-weaning survival and weight gain, and to provide practical guidance on fostering low-birth-weight piglets, we analyzed piglet survival and weight gain in litters of piglets from 52 sows followed through eight consecutive parities. Litters with high variation in birth weight had more deaths, especially if the litter’s mean birth weight was low. High variation in birth weight was also associated with high variation in weaning weight, but was not significantly related to mean weaning weight. Piglets with birth weights well below the range of most of the litter (‘low-birth-weight piglets’) …
Involvement Of Platelet-Derived Growth Factor, Pdgf Receptor Signaling, Focal Adhesion Kinase And Src In Pressure-Induced Vascular Smooth Muscle Hypertrophy, Darian Clark Rice
Involvement Of Platelet-Derived Growth Factor, Pdgf Receptor Signaling, Focal Adhesion Kinase And Src In Pressure-Induced Vascular Smooth Muscle Hypertrophy, Darian Clark Rice
Theses and Dissertations in Biomedical Sciences
Elevated blood pressure is associated with varying degrees of arterial remodeling. The mechanisms by which extracellular mechanical stress is converted into intracellular alterations in signal transduction and gene expression have yet to be fully elucidated. Our goal was to investigate the early events in the vascular smooth muscle response to acute hypertension and to identify mediators involved in long-term hypertensive remodeling.
In the acute phase of hypertension we targeted cell surface integrin and growth factor receptors thought to be mechanically sensitive. The signaling molecules FAK, Src and ERK-MAPK are known to be triggered by integrin engagement and growth factor receptor …
Terminal Deoxynucleotidyl Transferase Generation Of Sequence Diversity On Plasmids, Qingbei Zhang
Terminal Deoxynucleotidyl Transferase Generation Of Sequence Diversity On Plasmids, Qingbei Zhang
Morehead State Theses and Dissertations
A thesis presented to the faculty of the College of Science and Technology at Morehead State University in partial fulfillment of the requirements for the Degree of Master of Science by Qingbei Zhang on June 19, 2002.
Expression Of Gp73, A Resident Golgi Membrane Protein, In Viral And Nonviral Liver Disease, Raleigh D. Kladney, Xiaoyen Cui, Gary A. Bulla, Elizabeth M. Brunt, Claus J. Fimmel
Expression Of Gp73, A Resident Golgi Membrane Protein, In Viral And Nonviral Liver Disease, Raleigh D. Kladney, Xiaoyen Cui, Gary A. Bulla, Elizabeth M. Brunt, Claus J. Fimmel
Faculty Research & Creative Activity
GP73 is a novel type II Golgi membrane protein of unknown function that is expressed in the hepatocytes of patients with adult giant-cell hepatitis (Gene 2000;249:53-65). Its expression pattern in human liver disease and the regulation of its expression in hepatocytes have not been systematically studied. The aims of the present study were to compare GP73 protein levels in viral and nonviral human liver disease and in normal livers, to identify its cellular sources, and to study the regulation of its expression in hepatoma cells in vitro. GP73 protein levels were quantitated in explant livers of patients with well-defined disease …
Expression Of Gp73, A Resident Golgi Membrane Protein, In Viral And Nonviral Liver Disease, Raleigh Kladney, Xiaoyen Cui, Gary Bulla, Elizabeth Brunt, Claus Fimmel
Expression Of Gp73, A Resident Golgi Membrane Protein, In Viral And Nonviral Liver Disease, Raleigh Kladney, Xiaoyen Cui, Gary Bulla, Elizabeth Brunt, Claus Fimmel
Faculty Research & Creative Activity
GP73 is a novel type II Golgi membrane protein of unknown function that is expressed in the hepatocytes of patients with adult giant-cell hepatitis (Gene 2000;249:53-65). Its expression pattern in human liver disease and the regulation of its expression in hepatocytes have not been systematically studied. The aims of the present study were to compare GP73 protein levels in viral and nonviral human liver disease and in normal livers, to identify its cellular sources, and to study the regulation of its expression in hepatoma cells in vitro. GP73 protein levels were quantitated in explant livers of patients with well-defined disease …
Mechanisms Of Autoantigen Cleavage During Cell Death, Xiwei Wu
Mechanisms Of Autoantigen Cleavage During Cell Death, Xiwei Wu
Loma Linda University Electronic Theses, Dissertations & Projects
Specific intracellular autoantigens targeted by autoantibodies in systemic autoimmune and chronic inflammatory diseases undergo posttranslational modifications, such as cleavage, during cell death that could potentially enhance their immunogenicity. In light of the increasing interest in the immunological consequences of defective clearance of apoptotic cells, we explored whether autoantigens cleaved during apoptosis undergo an additional wave of proteolysis as apoptosis progresses to secondary necrosis in the absence of phagocytosis. Jurkat T cells treated with different apoptosis inducers underwent a rapid apoptosis that gradually progressed to secondary necrosis. During the initial apoptotic stages, several nuclear autoantigens, including PARP, Topo I, and LEDGF/p75 …
Inducible Gene Expression In Cell Cultures And In Microencapsulated Cells, Yong Yu
Inducible Gene Expression In Cell Cultures And In Microencapsulated Cells, Yong Yu
Loma Linda University Electronic Theses, Dissertations & Projects
The mifepristone-regulated transcriptional activation system provides a means to exogenously control gene expression in transformed mammalian cells in a temporal and spatial fashion. Such a promoter activation system consists of three components: The first of these is a steroidal inducer drug, mifepristone. This drug binds to the second component, a chimeric transcription factor complex, consisting of the mutant human progesterone receptor fused to the yeast GAL4 DNA-binding domain and the Herpes simplex virus protein VP 16 activation domain. The third component is a synthetic promoter, consisting of a series of GAL4 recognition sequences upstream of the adenovirus major late E1B …
The Effect Of Butyrate Feeding On Skeletal Muscle And Adipose Tissue Glucose Uptake, Sean Eric Thatcher
The Effect Of Butyrate Feeding On Skeletal Muscle And Adipose Tissue Glucose Uptake, Sean Eric Thatcher
Morehead State Theses and Dissertations
A thesis presented to the faculty of the College of Science and Technology at Morehead State University in partial fulfillment of the requirements for the Degree of Master of Science in Biology by Sean Eric Thatcher on May 31, 2002.
Searching For The Middle Ground: Mechanisms Of Chromosome Alignment During Mitosis, Tarun M. Kapoor, Duane A. Compton
Searching For The Middle Ground: Mechanisms Of Chromosome Alignment During Mitosis, Tarun M. Kapoor, Duane A. Compton
Dartmouth Scholarship
The contributions of key molecules predicted to align chromosomes at the center of the mitotic spindle have been recently examined. New results dictate that models for how chromosomes align during the early stages of mitosis must be revised to integrate properties of microtubule-based motor proteins as well as microtubule dynamics.
Construction Of Rhas And Rhar Overexpression Plasmids And The Effects Of Crp Mutants On E.Coli L-Rhamnose Gene Expression, Amber Bromenshenkel, Susan Egan
Construction Of Rhas And Rhar Overexpression Plasmids And The Effects Of Crp Mutants On E.Coli L-Rhamnose Gene Expression, Amber Bromenshenkel, Susan Egan
Honors Capstones
Capstone submitted as a graduation requirement for the BSU Honors Program.
The Role Of The Arabidopsis Phosphatidylinositol 3-Kinase In Vacuolar Protein Transport, Christopher A. Jones
The Role Of The Arabidopsis Phosphatidylinositol 3-Kinase In Vacuolar Protein Transport, Christopher A. Jones
All Graduate Theses and Dissertations, Spring 1920 to Summer 2023
In all eukaryotic organisms vesicle-mediated protein transport is crucial for maintaining cellular homeostasis. Over the past decade significant strides have been made in elucidating the molecular mechanisms governing this complex process. Both genetic and biochemical studies have demonstrated the unequivocal involvement of class III phospatidylinositol 3-kinases (PtdIns 3-kinases) in regulating vesicle transport. While PtdIns 3-kinases have been well studied in both yeast and mammalian systems, the role of these enzymes in plants is poorly understood. In the present study, we demonstrate that the Arabidopsis Ptdlns 3-kinase is localized to the cytoplasm, and perhaps the Golgi apparatus. Moreover, we show that …
Composition And Method For The Prevention And Treatment Of Oxidative Damage In Ocular Tissues, Marjorie F. Lou, Nalini Raghavachari;, Fengyu Qiao
Composition And Method For The Prevention And Treatment Of Oxidative Damage In Ocular Tissues, Marjorie F. Lou, Nalini Raghavachari;, Fengyu Qiao
School of Veterinary and Biomedical Sciences: Faculty Publications
Thioltransferase and derivatives thereof are provided. Methods of treating or preventing cataract formation comprosing administering thioltransferase or a derivative thereof are also provided. Thioltransferase or derivatives thereof are also useful for treating or preventing diseases resulting from or associated with oxidative stress. Human lens thioltransferase and a DNA sequence encoding the same are also provided.
Comparison Of Tnf-A Levels Produced By Macrophages Treated With Brucella Abortus And Escherichia Coli Lps, Tajie Harris
Comparison Of Tnf-A Levels Produced By Macrophages Treated With Brucella Abortus And Escherichia Coli Lps, Tajie Harris
Honors Capstones
Capstone submitted as a graduation requirement for the BSU Honors Program.
Determination Of Nuclear Factor-Kappa B Activation In Cultured Renal Epithelial Cells And Cardiac Myocytes Exposed To Cocaine And Morphine, David Angeles Tiangco
Determination Of Nuclear Factor-Kappa B Activation In Cultured Renal Epithelial Cells And Cardiac Myocytes Exposed To Cocaine And Morphine, David Angeles Tiangco
Biological Sciences Theses & Dissertations
Nuclear factor-kappa B (NF-kB) is an important transcription factor that participates in the genetic regulation of inflammation in many tissues. Cocaine and heroin are drugs of abuse associated with renal and cardiac pathology. The purpose of this study was to test the hypothesis that exposure to cocaine or morphine (a metabolite of heroin) would activate NF-kB in renal epithelial cells (COS-7) and cardiac myocytes (H9c2) grown in culture. COS-7 and H9c2 cells were co-transfected with an experimental reporter specific for NF-kB activation and a control reporter with constitutive activity. A dual-luciferase assay was used to determine levels of NF-kB activation …
A Cycle Of Vam7p Release From And Ptdins 3-P–Dependent Rebinding To The Yeast Vacuole Is Required For Homotypic Vacuole Fusion, Christine Boeddinghaus, Alexey J. Merz, Rico Laage, Christian Ungermann
A Cycle Of Vam7p Release From And Ptdins 3-P–Dependent Rebinding To The Yeast Vacuole Is Required For Homotypic Vacuole Fusion, Christine Boeddinghaus, Alexey J. Merz, Rico Laage, Christian Ungermann
Dartmouth Scholarship
Vacuole fusion requires a coordinated cascade of priming, docking, and fusion. SNARE proteins have been implicated in the fusion itself, although their precise role in the cascade remains unclear. We now report that the vacuolar SNAP-23 homologue Vam7p is a mobile element of the SNARE complex, which moves from an initial association with the cis-SNARE complex via a soluble intermediate to the docking site. Soluble Vam7p is specifically recruited to vacuoles and can rescue a fusion reaction poisoned with antibodies to Vam7p. Both the recombinant Vam7p PX domain and a FYVE domain construct of human Hrs block the recruitment of …
Prostate Specific Membrane Antigen (Psma): Immunoassay Development And Characterization Of Transcriptional Regulation, Zhen Xiao
Theses and Dissertations in Biomedical Sciences
Prostate cancer (PCA) is the most common cancer and the second leading cause of death among American men. The high mortality is greatly attributed to the lack of early detection tools and effective treatment for metastasis and relapses. Biomarkers that can discriminate benign from malignant tumor and signal the development of androgen independent and metastatic tumor are needed. A biomarker designated prostate specific membrane antigen (PSMA) has the potential to fulfill this need. The objective of this study is to develop a clinically useful immunoassay for quantitation of serum PSMA and to study the molecular mechanism underlying the upregulation of …
Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky
Ube1l Is A Retinoid Target That Triggers Pml/Rarα Degradation And Apoptosis In Acute Promyelocytic Leukemia, Sutisak Kitareewan, Ian Pitha-Rowe, David Sekula, Christopher H. Lowrey, Michael J. Nemeth, Todd R. Golub, Sarah J. Freemantle, Ethan Dmitrovsky
Dartmouth Scholarship
All-trans-retinoic acid (RA) treatment induces remissions in acute promyelocytic leukemia (APL) cases expressing the t(15;17) product, promyelocytic leukemia (PML)/RA receptor α (RARα). Microarray analyses previously revealed induction of UBE1L (ubiquitin-activating enzyme E1-like) after RA treatment of NB4 APL cells. We report here that this occurs within 3 h in RA-sensitive but not RA-resistant APL cells, implicating UBE1L as a direct retinoid target. A 1.3-kb fragment of the UBE1L promoter was capable of mediating transcriptional response to RA in a retinoid receptor-selective manner. PML/RARα, a repressor of RA target genes, abolished this UBE1L promoter activity. A hallmark of …
Osmosensitive Release Of Neurotransmitter Amino Acids: Relevance And Mechanisms, Herminia Pasantes-Morales, Rodrigo Franco, Lenin Ochoa, Benito Ordaz
Osmosensitive Release Of Neurotransmitter Amino Acids: Relevance And Mechanisms, Herminia Pasantes-Morales, Rodrigo Franco, Lenin Ochoa, Benito Ordaz
School of Veterinary and Biomedical Sciences: Faculty Publications
Hyposmolarity activates amino acid efflux as part of the corrective volume process in a variety of cells. This review discusses the mechanism of amino acid release in brain cells preparations. Results present evidence of substantial differences between the efflux of taurine and that of GABA and glu-tamate, which besides a possible role as osmolytes, have a main function as synaptic transmitters. The differences found concern the efflux time course, the sensitivity to Cl– channel blockers, the modulation by tyrosine kinases, the influence of PKC and the effect of cytoskeleton disruptive agents. While taurine efflux features fit well with the …
A Mechanistic Study Of Myoglobin Nephrotoxicity, Jennifer L. Minigh
A Mechanistic Study Of Myoglobin Nephrotoxicity, Jennifer L. Minigh
Theses, Dissertations and Capstones
Myoglobin is an endogenous protein that can become nephrotoxic under certain conditions such as crush injuries, drug overdose, and seizures where prolonged contraction of muscle leads to cell death and leakage of myoglobin. The mechanism of myoglobin-induced nephrotoxicity is not fully understood. The purpose of this study was to characterize the sequence and mechanistic events associated with the in vitro toxicity of myoglobin in renal cortical slices. Renal tissue was isolated from Fischer 344 rats. Slices of renal cortex were prepared by freehand. These slices were then incubated for 60-180 minutes with myoglobin (0-12 mg/mL) pretreated with 4 mM ascorbic …
Pkcα Translocation And Actin Remodeling In Contracting A7r5 Smooth Muscle Cells, Chenwei Li
Pkcα Translocation And Actin Remodeling In Contracting A7r5 Smooth Muscle Cells, Chenwei Li
Theses, Dissertations and Capstones
Recent research indicates that protein kinase C (PKC) plays an important role in smooth muscle contraction. Because PKC activation and specificity of substrate phosphorylation is believed to be associated with the relocalization of the enzyme to specific cell sites, we first investigated the subcellular translocation of PKCα in A7r5 smooth muscle cells by confocal microscopy through use of standard immunohistologic staining and PKCα - enhanced green fluorescent protein (PKCα -EGFP) fusion protein expression. PKCα was diffusely distributed throughout the cytosol in the unstimulated A7r5 cell. Upon stimulation with phorbol 12, 13 dibutyrate (PDBu), PKCα was translocated primarily to either the …
Actin And Myosin Remodeling In The A7r5 Smooth Muscle Cell, Michael E. Fultz
Actin And Myosin Remodeling In The A7r5 Smooth Muscle Cell, Michael E. Fultz
Theses, Dissertations and Capstones
Active remodeling of the cytoskeleton has been proposed to contribute to the low energy cost and maintenance of the sustained contraction in smooth muscle. Using confocal microscopy and standard immunohistochemical techniques, direct observation of actin remodeling was studied in the contracting A7r5 cell in response to the diacylglycerol (DAG) analog phorbol 12, 13 dibutyrate (PDBu). -actin was shown to exist in the resting cell as parallel stress cables that extend across the cell. Stimulation by PDBu resulted in a sustained contraction that occurred in approximately eighty-five percent of the A7r5 cells. The initial contraction was not uniform, but primarily occurred …
Actin Dynamics Regulate Myosin Assembly In Muscle Cells, John Dylan Cook
Actin Dynamics Regulate Myosin Assembly In Muscle Cells, John Dylan Cook
Inquiry: The University of Arkansas Undergraduate Research Journal
During muscle cell (i.e. myocyte )development, organization of actin and myosin into the contractile unit (i.e. sarcomere) is required for proper muscle contraction. By disrupting the processes of muscle cell development, I am able to see which steps play important roles in proper maturation of myocytes. Elucidation of the key pathways in muscle development could lead to a better understanding of human cardiac hypertrophies and muscle myopathies. Since actin filament formation precedes myosin organization, I am using actin assembly inhibitors to determine if actin filaments are a necessary prerequisite for myosin organization. It is hypothesized that disruption of actin will …
The Osteopetrotic Mutation Toothless (Tl) Is A Loss-Of-Function Frameshift Mutation In The Rat Csf1 Gene: Evidence Of A Crucial Role For Csf-1 In Osteoclastogenesis And Endochondral Ossification, Liesbeth Van Wesenbeeck, Paul R. Odgren, Carole A. Mackay, Marina D'Angelo, Fayez F. Safadi, Steven N. Popoff, Wim Van Hul, Sandy C. Marks Jr.
The Osteopetrotic Mutation Toothless (Tl) Is A Loss-Of-Function Frameshift Mutation In The Rat Csf1 Gene: Evidence Of A Crucial Role For Csf-1 In Osteoclastogenesis And Endochondral Ossification, Liesbeth Van Wesenbeeck, Paul R. Odgren, Carole A. Mackay, Marina D'Angelo, Fayez F. Safadi, Steven N. Popoff, Wim Van Hul, Sandy C. Marks Jr.
PCOM Scholarly Works
The toothless (tl) mutation in the rat is a naturally occurring, autosomal recessive mutation resulting in a profound deficiency of bone-resorbing osteoclasts and peritoneal macrophages. The failure to resorb bone produces severe, unrelenting osteopetrosis, with a highly sclerotic skeleton, lack of marrow spaces, failure of tooth eruption, and other pathologies. Injections of CSF-1 improve some, but not all, of these. In this report we have used polymorphism mapping, sequencing, and expression studies to identify the genetic lesion in the tl rat. We found a 10-base insertion near the beginning of the open reading of the Csf1 gene that yields a …