Rescue of developmental lens abnormalities in chimaeras of noncataractous and congenital cataractous mice

Development ◽  
1987 ◽  
Vol 99 (4) ◽  
pp. 473-480
Author(s):  
A.L. Muggleton-Harris ◽  
K. Hardy ◽  
N. Higbee
Keyword(s):  
Medical Research ◽  
Congenital Cataract ◽  
Biochemical Analysis ◽  
Growth Regulation ◽  
Cellular Level ◽  
Model System ◽  
Mouse Mutant ◽  
Phenotypic Characteristics ◽  
Cataractous Lens ◽  
Mouse Lens

In the study of the lens of a congenital cataractous mouse mutant (CAT), it has been shown that a loss of growth regulation at the cellular level causes gross lens abnormalities. The phenotypic characteristics of the cataractous mouse lens are similar to those seen in human congenital cataract and thus serves as a model system for medical research. In this present investigation, we have demonstrated that the abnormalities of the congenital cataractous lens can be rescued by forming chimaeras between DBA/2 (a noncataractous strain of mouse) and the CAT mutant. This report describes the histological, cellular and biochemical analysis of the resultant chimaeric eyes, and discusses possible mechanisms by which these results were achieved.

Organization and composition of the cytoskeleton of giant algal cells: Its role in wound healing

1989 ◽  
Vol 47 ◽  
pp. 752-753
Author(s):  
R. H. Goddard ◽  
J. W. La Claire II
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Wound Healing ◽  
Light Microscopy ◽  
Cellular Level ◽  
Model System ◽  
Functional Roles ◽  
Transmission Electron ◽  
New Findings ◽  
Secondary Antibodies

We have been using the giant algal cells of Ernodesmis verticillata as a model system to study the process of wound healing at the cellular level of organization. Using immuno-localization techniques we have observed changes in the distribution of tubulin-containing microtubules (MTs) and actin-containing microfilaments (MFs), that occur during wound healing. Based on these and new findings, we carried out correlative experiments with inhibitors to investigate the functional roles of the various cytoskeletal components in wound healing.Emodesmis cells were cultured, Wounded and Fixed as described previously. The cytoplasm from fixed cells was adhered to polylysine-coated coverslips for light microscopy, or to formvar coated gold grids for transmission electron microscopy (TEM).The attached cells were labeled with primary antibodies (against tubulin ,actin,calmodulin [CAM], intermediate filament [If] proteins, or myosin)followed by incubation in appropriate secondary antibodies conjugated with FITC or TRITC for fluorescence, or conjugated to gold beads for TEM.

scholarly journals Two Distinct Pathways for Targeting Proteins from the Cytoplasm to the Vacuole/Lysosome

1997 ◽  
Vol 139 (7) ◽  
pp. 1687-1695 ◽  
Author(s):  
Misuzu Baba ◽  
Masako Osumi ◽  
Sidney V. Scott ◽  
Daniel J. Klionsky ◽  
Yoshinori Ohsumi
Keyword(s):  
Biosynthetic Pathway ◽  
Biochemical Analysis ◽  
Protein Transport ◽  
Cellular Level ◽  
Spherical Particles ◽  
Alternate Pathway ◽  
Membrane Bound ◽  
Growing Conditions ◽  
Starvation Conditions ◽  
Intracellular Structure

Stress conditions lead to a variety of physiological responses at the cellular level. Autophagy is an essential process used by animal, plant, and fungal cells that allows for both recycling of macromolecular constituents under conditions of nutrient limitation and remodeling the intracellular structure for cell differentiation. To elucidate the molecular basis of autophagic protein transport to the vacuole/lysosome, we have undertaken a morphological and biochemical analysis of this pathway in yeast. Using the vacuolar hydrolase aminopeptidase I (API) as a marker, we provide evidence that the autophagic pathway overlaps with the biosynthetic pathway, cytoplasm to vacuole targeting (Cvt), used for API import. Before targeting, the precursor form of API is localized mostly in restricted regions of the cytosol as a complex with spherical particles (termed Cvt complex). During vegetative growth, the Cvt complex is selectively wrapped by a membrane sac forming a double membrane-bound structure of ∼150 nm diam, which then fuses with the vacuolar membrane. This process is topologically the same as macroautophagy induced under starvation conditions in yeast (Baba, M., K. Takeshige, N. Baba, and Y. Ohsumi. 1994. J. Cell Biol. 124:903–913). However, in contrast with autophagy, API import proceeds constitutively in growing conditions. This is the first demonstration of the use of an autophagy-like mechanism for biosynthetic delivery of a vacuolar hydrolase. Another important finding is that when cells are subjected to starvation conditions, the Cvt complex is now taken up by an autophagosome that is much larger and contains other cytosolic components; depending on environmental conditions, the cell uses an alternate pathway to sequester the Cvt complex and selectively deliver API to the vacuole. Together these results indicate that two related but distinct autophagy-like processes are involved in both biogenesis of vacuolar resident proteins and sequestration of substrates to be degraded.

scholarly journals Dictyostelium discoideum as a pharmacological model system to study the mechanisms of medicinal drugs and natural products

2019 ◽  
Vol 63 (8-9-10) ◽  
pp. 541-550 ◽  
Author(s):  
Judith Schaf ◽  
Joseph Damstra-Oddy ◽  
Robin S.B. Williams
Keyword(s):  
Natural Products ◽  
Dictyostelium Discoideum ◽  
Cellular Level ◽  
Model System ◽  
Genetic Redundancy ◽  
Therapeutic Drugs ◽  
Pharmacologically Active ◽  
Medicinal Drugs ◽  
Pharmacological Model ◽  
Active Natural

Developing novel compounds for the treatment of diseases remains one of the highest priorities in biomedical research, where it is critical to identify their targets and how they work at a cellular level. Most studies in this area employ mammalian models, since rodents or non-human primates are seen as a good approximation for humans. However, using mammalian models can be problematic for a range of reasons, including high genetic redundancy and the essential role for many proteins in development. More importantly, it is very difficult to identify how compounds function at a cellular or molecular level in these models without a previously suggested mechanism or target. So how can we identify targets of medicinal compounds? In this review we outline the use of an innovative and tractable model system, Dictyostelium discoideum, to provide useful insight to the cellular and molecular functions of both therapeutic drugs and pharmacologically active natural products. We outline the advantages of using this model, and then provide a range of exemplar studies using D. discoideum in pharmacological research to demonstrate breakthroughs in understanding the action and effects of compounds, and the subsequent translational of these advances to mammalian models leading to potential improvements in societal health.

scholarly journals LIPID DEFICIENCIES, LEUKOCYTOSIS, BRITTLE SKIN—A LETHAL SYNDROME CAUSED BY A RECESSIVE MUTATION, EDEMATOUS (OED), IN THE MOUSE

Genetics ◽  
1975 ◽  
Vol 81 (3) ◽  
pp. 525-536
Author(s):  
Michael B Schiffman ◽  
Maria L Santorineou ◽  
Susan E Lewis ◽  
Howard A Turchin ◽  
Salome Gluecksohn-Waelsch
Keyword(s):  
Lipid Metabolism ◽  
Serum Lipids ◽  
Autosomal Recessive ◽  
Biochemical Analysis ◽  
Liver Cholesterol ◽  
Recessive Mutation ◽  
Phenotypic Characteristics ◽  
Normal Limits ◽  
Mode Of Inheritance ◽  
Severe Disturbance

ABSTRACT A new neonatal lethal mutation in the mouse with pleiotropic effects, edematous (oed), arose spontaneously in the phocomelic strain and has been shown to have an autosomal recessive mode of inheritance. The external phenotypic characteristics include a generally bloated appearance, shiny cellophane-like skin, and distal hematomata of the extremities. Internally, no gross or histological abnormalities could be identified, with the exception of a striking leukocytosis. Biochemical analysis revealed a severe disturbance of lipid metabolism. Deficiencies in the VLDL, LDL, and the HDL lipoprotein fractions have been found in the mutant plasma. In addition, all serum lipids are markedly decreased. However, in the mutant liver, only triglycerides are significantly decreased; total liver cholesterol and phospholipid values are within normal limits. The primary biochemical defect as well as the causal relationship between the striking abnormalities of lipid metabolism and those of skin and blood are unknown at this time.

scholarly journals A gene location for the inheritance of the Cataract Fraser (CatFr) mouse congenital cataract

1987 ◽  
Vol 49 (3) ◽  
pp. 235-238 ◽  
Author(s):  
A. L. Muggleton-Harris ◽  
M. F. W. Festing ◽  
M. Hall
Keyword(s):  
Animal Models ◽  
Medical Research ◽  
Genetic Background ◽  
Congenital Cataract ◽  
Gene Location ◽  
Chromosome 10 ◽  
Molecular Aspects

SummaryAnimal models which emulate defects similar to those in man are required for medical research. Many investigations on the cellular, developmental and molecular aspects of cataractogenesis use the cataract Fraser (CatFr) mouse. This report shows that the CatFT and Lop lens abnormalities are linked, and are probably allelic genes on chromosome 10. It also shows that the CatFT gene is maintained on an inbred genetic background which differs from 79 other strains; it is proposed that this strain be named CAT.

scholarly journals Lens opacity: a new gene for congenital cataract on chromosome 10 of the mouse

1981 ◽  
Vol 38 (3) ◽  
pp. 337-341 ◽  
Author(s):  
Mary F. Lyon ◽  
Susan E. Jarvis ◽  
Irene Sayers ◽  
Roger S. Holmes
Keyword(s):  
Congenital Cataract ◽  
New Method ◽  
Lens Opacity ◽  
Mutation Rates ◽  
Mouse Mutant ◽  
Chromosome 10 ◽  
Point Of Interest ◽  
New Gene ◽  
Medical Importance ◽  
Mutant Genes

Mouse mutant genes which result in defects similar to those of medical importance in man may be of value as models for the study of the defect concerned. We report here a new gene causing congenital cataract in the mouse, which may be useful in the understanding of cataract in man.A further point of interest is that Kratochvilova & Ehling (1979) have recently developed a new method of measuring increased mutation rates in the mouse, by examining offspring of animals treated with mutagens for the presence of cataracts due to mutant genes. For the purposes of this test it is valuable to have information on the number and map position of loci which can mutate to give cataracts.

Chronic Myelogenous Leukemia as a Model System for Stem Cell Growth Regulation and Hematolymphoid Development

1986 ◽  
pp. 657-663
Author(s):  
Owen N. Witte ◽  
Jami McLaughlin ◽  
Ann-Marie Mes-Masson ◽  
Michael Timmons ◽  
Steven Clark ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Growth ◽  
Chronic Myelogenous Leukemia ◽  
Growth Regulation ◽  
Model System ◽  
Myelogenous Leukemia ◽  
Cell Growth Regulation

Matrix Metalloproteinase in Mammary Gland Remodeling-Modulation by Glycosaminoglycans

1999 ◽  
Vol 19 (5) ◽  
pp. 485-490 ◽  
Author(s):  
P. R. Sudhakaran ◽  
M. Ambili ◽  
Susy Philip
Keyword(s):  
Mammary Gland ◽  
Basement Membrane ◽  
Biochemical Analysis ◽  
Mammary Gland Development ◽  
Adult Life ◽  
Selective Inhibition ◽  
Model System ◽  
Matrix Components ◽  
Gland Development

Mammary gland which undergoes proliferation, differentiation and involution in adult life is a useful model system to study the role of extracellular matrix (ECM) in regulating tissue specific functions. The involution that follows weaning results in the suppression of casein gene expression, collapse of alveolar structures and degradation of basement membrane as evidenced by biochemical analysis of matrix components like proteoglycans and collagen. Differential expression of three different MMPs viz. 130 K, 68 K and 60 K with varying specificity to Col IV of basement membrane and Col I of stroma, their selective inhibition by TIMP and proteoglycans and modulation by estrogen highlight the importance of these in the remodeling of the ECM in the mammary gland. The inhibition of these MMPs by glycosaminoglycans, particularly CS and change in the concentration of CS at different stages of mammary gland development suggests the existence of a novel mechanism for the regulation of the activity of MMPs at extracellular sites.

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