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Anti-Idiotype Monoclonal Antibody 1a7 And Use For The Treatment Of Melanoma And Small Cell Carcinoma, Malaya Chatterjee, Kenneth A. Foon Mar 1997

Anti-Idiotype Monoclonal Antibody 1a7 And Use For The Treatment Of Melanoma And Small Cell Carcinoma, Malaya Chatterjee, Kenneth A. Foon

Microbiology, Immunology and Molecular Genetics Faculty Patents

The present invention relates isolation of anti-idiotypic antibody 1A7 raised against anti-GD2 mAb 14G2a and its use for the treatment of melanoma and small cell carcinoma. The antibody may be used as a substitute for isolated purified GD2 antigen in any appropriate application.


Update - March 1997, Loma Linda University Center For Christian Bioethics Mar 1997

Update - March 1997, Loma Linda University Center For Christian Bioethics

Update

In this issue:

-- James Walters publishes book on Personhood
-- Prayer and Health Care: An "Altared" Responsibility
-- Conference Report on "Bioethics and Human Destiny: Jewish and Christian Perspectives"


Transgenic Mice Which Overexpress Nerve Growth Factor, Kathryn M. Albers, Brian M. Davis Feb 1997

Transgenic Mice Which Overexpress Nerve Growth Factor, Kathryn M. Albers, Brian M. Davis

Neuroscience Faculty Patents

Transgenic mice that express increased levels of nerve growth factor (NGF) in the epidermis and other stratified, keratinized epithelium. The nerve growth factor expressing transgenic mice are useful in the study of neurodegenerative disorders of the brain such as Parkinson's syndrome and Alzheimer's disease and for testing for drug candidates for the treatment of these diseases.


Aspartate 19 And Glutamate 121 Are Critical For Transport Function Of The Myo-Inositol/H+ Symporter From Leishmania Donovani, Andreas Seyfang, Michael Kavanaugh, Scott M. Landfear Jan 1997

Aspartate 19 And Glutamate 121 Are Critical For Transport Function Of The Myo-Inositol/H+ Symporter From Leishmania Donovani, Andreas Seyfang, Michael Kavanaugh, Scott M. Landfear

Biomedical and Pharmaceutical Sciences Faculty Publications

The protozoan flagellate Leishmania donovani has an active myo-inositol/proton symporter (MIT), which is driven by a proton gradient across the parasite membrane. We have used site-directed mutagenesis in combination with functional expression of transporter mutants in Xenopusoocytes and overexpression in Leishmania transfectants to investigate the significance of acidic transmembrane residues for proton relay and inositol transport. MIT has only three charged amino acids within predicted transmembrane domains. Two of these residues, Asp19 (TM1) and Glu121 (TM4), appeared to be critical for transport function of MIT, with a reduction of inositol transport to about 2% of wild-type …


Regulation Of The Ncx1 Gene In The Normal And Hypertrophied Myocardium, Kimberly Victoria Barnes Jan 1997

Regulation Of The Ncx1 Gene In The Normal And Hypertrophied Myocardium, Kimberly Victoria Barnes

MUSC Theses and Dissertations

The sodium-calcium exchanger (NCX1) plays a major role in calcium efflux, and therefore, in calcium homeostasis in the heart. The exchanger mRNA and protein is rapidly upregulated within one hour of pressure overload. In this work, the exchanger has been shown to be upregulated by persistent pressure overload for at least one to two weeks. The 5' end of the NCX1 gene has been characterized in order to examine transcriptional regulation of the cardiac promoter. Four feline NCX1 isoforms of the 5' untranslated region have been cloned: one from brain (Br1), one from kidney (K1), and two from heart (H1 …


Dexamethasone Decreases Cell-Cell Adhesion In The 235-1 Pituitary Tumor Cell Line, Phillip Richard Spangler Jan 1997

Dexamethasone Decreases Cell-Cell Adhesion In The 235-1 Pituitary Tumor Cell Line, Phillip Richard Spangler

Theses, Dissertations and Capstones

Physical contacts between cells are known to influence a broad range of biological activities. Investigations into the regulation of prolactin gene expression have shown that cell behavior within the pituitary may also be affected by adhesive contacts. To better understand the mechanisms that regulate cell-cell adhesive contacts in these endocrine cells, we developed a procedure that quantitatively assays homotypic aggregation in the rat pituitary tumor cell line, 235-1. We observed that treatment of 235-1 cells with dexamethasone (Dex), a synthetic glucocorticoid, not only reduces prolactin production but also decreases the reformation of cell-cell contacts. In two independent experiments, control cells …


The Role Of Fas And Fas Ligand In Apoptosis During Regression Of The Corpus Luteum, Sharon Roughton Jan 1997

The Role Of Fas And Fas Ligand In Apoptosis During Regression Of The Corpus Luteum, Sharon Roughton

Theses : Honours

Apoptosis, a form of physiological cell death, has been found to occur during regression of the corpus luteum (Juengel etal, 1993; Dharmarajan etal, 1994). The pathways involved in this process, however, have yet to be specified. One possible mediator of corpus luteum regression is the Fas (or AP0-1 or CD95) receptor, a transmembrane protein which induces apoptosis in the cell when ligated. In order to further confirm this hypolhesis, the present study establishes and quantitates the presence and regulation of Fas receptor and Fas ligand (Fasl) in the rat corpus luteum during pregnancy and post-partum. The animals used were sexually …


The Isolation And Characterization Of Plv22a, A Mobilizable Plasmid From Bacteroides Fragilis, Thomas Joseph Novicki Jan 1997

The Isolation And Characterization Of Plv22a, A Mobilizable Plasmid From Bacteroides Fragilis, Thomas Joseph Novicki

Dissertations

No abstract provided.


Role Of Tgf-† In Heart Development: Analysis Of The Type Ii Tgf-† Receptor, Patricia S. Grutkoski Jan 1997

Role Of Tgf-† In Heart Development: Analysis Of The Type Ii Tgf-† Receptor, Patricia S. Grutkoski

Dissertations

No abstract provided.


Faculty Publications 1996, Lsu Health Sciences Center New Orleans Jan 1997

Faculty Publications 1996, Lsu Health Sciences Center New Orleans

Historical Faculty Publications

This Faculty bibliography contains 734 publications.


Method For Obtaining Antifungal And Herbicidal Compounds That Target The First Committed Step In Shingolipid Long-Chain Base Biosynthesis, Robert C. Dickson, Robert L. Lester Dec 1996

Method For Obtaining Antifungal And Herbicidal Compounds That Target The First Committed Step In Shingolipid Long-Chain Base Biosynthesis, Robert C. Dickson, Robert L. Lester

Molecular and Cellular Biochemistry Faculty Patents

The invention provides the LCB1 and LCB2 genes of the yeast Saccharomyces cerevisiae that encode subunits of the enzyme serine palmitoyltransferase (SPT), the first enzyme leading to synthesis of the long-base component of the sphingolipids. The present specification describes the isolation of the LCB1 and LCB2 genes. The invention further relates to methods of using these genes to either inhibit SPT activity or to inhibit synthesis of the enzyme. Furthermore, the invention relates to methods for constructing strains of S. cerevisiae or other organisms that can be used to select and to test for compounds that either inhibit SPT activity …


A Comparison Of Olfactory Organ Development And Feeding Behavior In Larval Fathead Minnows, Pimephales Promelas Rafinesque, Robert Molloy Dec 1996

A Comparison Of Olfactory Organ Development And Feeding Behavior In Larval Fathead Minnows, Pimephales Promelas Rafinesque, Robert Molloy

Masters Theses & Specialist Projects

The early recruitment and use of the chemoreceptive senses, olfaction and gustation, are important for early behavior development in fathead minnows and the ability of larvae to survive after hatching. Chemoreception is used in the location of food, avoidance of predators, and for intraspecific communication. Furthermore, some studies have shown the olfactory system to be adversely impacted by environmental contaminants and low pH. Since the fathead minnow is a commercially raised baitfish in the aquaculture industry, and serves as a standard test organism for bioassays and reaction studies of aquatic contamination by the United States Environmental Protection Agency, an understanding …


Method And Compositions For Treating Age Related Disorders, John M. Carney, Robert A. Floyd Nov 1996

Method And Compositions For Treating Age Related Disorders, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Compositions containing as the active ingredient a spin-trapping reagent, preferably α-phenyl butyl nitrone (PBN) or spin-trapping derivatives thereof, in a suitable pharmaceutical carrier for administration to a patient are disclosed for treating or preventing symptoms associated with aging or other conditions associated with oxidative tissue damage. Other spin-trapping agents can also be used, such as 5,5-dimethyl pyrroline N-oxide (DMPO) or α-(4-pyridyl 1-oxide)-N-tert-butylnitrone (POBN), and other spin-trapping derivatives thereof. These compositions and methods are useful in the treatment of age-related disorders, pre-surgical and/or pre-anesthetic preparation or administration of chemotherapeutic agents, and in the treatment of disorders or trauma of the brain, …


Cellular Basis Of Decreased Immune Responses To Pneumococcal Vaccines In Aged Mice, Manju Garg, Wei Luo, Alan M. Kaplan, Subbarao Bondada Nov 1996

Cellular Basis Of Decreased Immune Responses To Pneumococcal Vaccines In Aged Mice, Manju Garg, Wei Luo, Alan M. Kaplan, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

Previously, model systems were developed in our laboratory to study murine immune responses to the 23-valent pneumococcal polysaccharide vaccine Pnu-Imune, both in vivo and in vitro (M. Garg and B. Subbarao, Infect. Immun. 60:2329-2336, 1992; M. Garg, A. M. Kaplan, and S. Bondada, J. Immunol. 152: 1589-1596, 1994). Using these systems, we found that aged mice did not respond to the vaccine in vivo or in vitro. Cell separation studies showed that the unresponsiveness of the aged spleen cells to the vaccine was not due to an intrinsic B-cell defect or to T-cell-mediated immunosuppression but resulted from an accessory cell …


Attachment Of Toxoplasma Gondii To Host Cells Is Host Cell Cycle Dependent., Jane Grimwood, Jose R. Mineo, Lloyd H. Kasper Oct 1996

Attachment Of Toxoplasma Gondii To Host Cells Is Host Cell Cycle Dependent., Jane Grimwood, Jose R. Mineo, Lloyd H. Kasper

Dartmouth Scholarship

The initial attachment of Toxoplasma tachyzoites to target host cells is an important event in the life cycle of the parasite and hence critical in the pathogenesis of this infection. The efficiency of Toxoplasma attachment to synchronized populations of Chinese hamster ovary cells and bovine kidney cells was investigated by using a glutaraldehyde-fixed host cell assay system. For both cell lines, parasite attachment increased as the synchronized host cells proceeded from the G1 phase to the mid-S phase and then decreased as the cells entered the G2-M boundary. Postulating that these differences in attachment reflect the upregulation of a specific …


Opposing Motor Activities Are Required For The Organization Of The Mammalian Mitotic Spindle Pole, Tirso Gaglio, Alejandro Saredi, James B. Bingham, M Josh Hasbani, Steven R. Grill, Trina A. Schroer, Duane A. Compton Oct 1996

Opposing Motor Activities Are Required For The Organization Of The Mammalian Mitotic Spindle Pole, Tirso Gaglio, Alejandro Saredi, James B. Bingham, M Josh Hasbani, Steven R. Grill, Trina A. Schroer, Duane A. Compton

Dartmouth Scholarship

We use both in vitro and in vivo approaches to examine the roles of Eg5 (kinesin-related protein), cytoplasmic dynein, and dynactin in the organization of the microtubules and the localization of NuMA (Nu-clear protein that associates with the Mitotic Apparatus) at the polar ends of the mammalian mitotic spindle. Perturbation of the function of Eg5 through either immunodepletion from a cell free system for assembly of mitotic asters or antibody microinjection into cultured cells leads to organized astral microtubule arrays with expanded polar regions in which the minus ends of the microtubules emanate from a ring-like structure that contains NuMA. …


Identification And Characterization Of The Thrombin Binding Sites On Fibrin, David A. Meh, Kevin R. Siebenlist, Michael W. Mosesson Sep 1996

Identification And Characterization Of The Thrombin Binding Sites On Fibrin, David A. Meh, Kevin R. Siebenlist, Michael W. Mosesson

Biomedical Sciences Faculty Research and Publications

Thrombin binds to fibrin at two classes of non-substrate sites, one of high affinity and the other of low affinity. We investigated the location of these thrombin binding sites by assessing the binding of thrombin to fibrin lacking or containing γ′ chains, which are fibrinogen γ chain variants that contain a highly anionic carboxyl-terminal sequence. We found the high affinity thrombin binding site to be located exclusively in D domains on γ′ chains (Ka, 4.9 × 106−1; n, 1.05 per γ′ chain), whereas the low affinity thrombin binding site was in the fibrin E …


The Protective Role Of Manganese Superoxide Dismutase Against Adriamycin-Induced Acute Cardiac Toxicity In Transgenic Mice, Hsiu-Chuan Yen, Terry D. Oberley, Satit Vichitbandha, Ye-Shih Ho, Daret K. St. Clair Sep 1996

The Protective Role Of Manganese Superoxide Dismutase Against Adriamycin-Induced Acute Cardiac Toxicity In Transgenic Mice, Hsiu-Chuan Yen, Terry D. Oberley, Satit Vichitbandha, Ye-Shih Ho, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Adriamycin (ADR) is a potent anticancer drug known to cause severe cardiac toxicity. Although ADR generates free radicals, the role of free radicals in the development of cardiac toxicity and the intracellular target for ADR-induced cardiac toxicity are still not well understood. We produced three transgenic mice lines expressing increased levels of human manganese superoxide dismutase (MnSOD), a mitochondrial enzyme, as an animal model to investigate the role of ADR-mediated free radical generation in mitochondria. The human MnSOD was expressed, functionally active, and properly transported into mitochondria in the heart of transgenic mice. The levels of copper-zinc SOD, catalase, and …


The Effects Of Lead Acetate On Host Susceptibility To Trypanosoma Cruzi, Tabitha Ellis Aug 1996

The Effects Of Lead Acetate On Host Susceptibility To Trypanosoma Cruzi, Tabitha Ellis

Masters Theses & Specialist Projects

Trypanosoma cruzi. a protozoan parasite, causes American trypanosomiasis or Chagas' disease. The infective stage of this parasite resides in the hindgut of the reduviid bug (family Reduviidae), which is both host and vector, and is transmitted to the mammalian host through fecal material released during a blood meal. Chagas' disease, an acute to chronic infection resulting in fever, malaise, and heart and liver enlargement, is becoming a concern in the United States due to the large increase in Latin American immigrants, and the lack of safe and effective therapeutic treatment and vaccination. Another growing concern in the United States involves …


Antibody Response To Heat Shock Proteins Of Trypanosoma Cruzi And Histopathology In Mice Infected And Maintained At Elevated Environmental Temperature, Ahmed Arif Aug 1996

Antibody Response To Heat Shock Proteins Of Trypanosoma Cruzi And Histopathology In Mice Infected And Maintained At Elevated Environmental Temperature, Ahmed Arif

Masters Theses & Specialist Projects

Trypanosoma cruzi is an obligate intracellular parasite infecting 18-20 million people in Latin America. It is the causative agent of Chagas' disease, commonly referred to as American Trypanosomiasis. The C3H murine model is widely used to study experimental Chagas' disease. It is well documented that when these highly susceptible mice are infected with the Brazil strain of T. cruzi and maintained at room temperature (RT), mice die between day 35-45 of infection. However, when held at an elevated temperature of 36°C, C3H mice survive an otherwise lethal infection with T. cruzi. When held at 36°C, the body temperature of the …


An Investigation Of Hexatylis Contracta Blomquist (Southern Heartleaf): Individuals, Hybrids, Populations And Species, Patrick Carroll Aug 1996

An Investigation Of Hexatylis Contracta Blomquist (Southern Heartleaf): Individuals, Hybrids, Populations And Species, Patrick Carroll

Masters Theses & Specialist Projects

Hexastylis contracta Blomquist is a rare herbaceous perennial plant endemic to southeastern North America. The plant exhibits a disjunct distribution, being found on the Cumberland Plateau of Tennessee and Kentucky and also 300 km east in the Blue Ridge Mountains of North Carolina. This plant was the subject of a population inventory supported through the Kentucky State Nature Preserves Commission (KNPC) which expanded the number of known populations of the species (28) by 68%, with 47 populations now known to exist. A morphological analysis of this species was done using principal components analysis. This analysis was used to answer questions …


Interleukin-10 Inhibits Tumor Metastasis Through An Nk-Cell Dependent Mechanism, Li-Mou Zheng, David M. Ojcius, F. Garaud, C. Roth, E. Maxwell, Z. Li, H. Rong, J. Chen, X. Y. Wang, J. J. Catino, I. King Aug 1996

Interleukin-10 Inhibits Tumor Metastasis Through An Nk-Cell Dependent Mechanism, Li-Mou Zheng, David M. Ojcius, F. Garaud, C. Roth, E. Maxwell, Z. Li, H. Rong, J. Chen, X. Y. Wang, J. J. Catino, I. King

All Dugoni School of Dentistry Faculty Articles

Interleukin-10 (IL-10) is a recently described pleiotropic cytokine secreted mainly by type 2 helper T cells. Previous studies have shown that IL-10 suppresses cytokine expression by natural killer (NK) and type 1 T cells, thus down-regulating cell-mediated immunity and stimulating humoral responses. We here report that injected IL-10 protein is an efficient inhibitor of tumor metastasis in experimental (B16-F10) and spontaneous (M27 and Lox human melanoma) metastasis models in vivo at doses that do not have toxic effects on normal or cancer cells. Histological characterization after IL-10 treatment confirmed the absence of CD8+ and CD4+ T cells and macrophages at …


Differential Expression Of The Toxr Regulon In Classical And E1 Tor Biotypes Of Vibrio Cholerae Is Due To Biotype-Specific Control Over Toxt Expression., Victor J. Dirita, Melody Neely, Ronald K. Taylor, Paul M. Bruss Jul 1996

Differential Expression Of The Toxr Regulon In Classical And E1 Tor Biotypes Of Vibrio Cholerae Is Due To Biotype-Specific Control Over Toxt Expression., Victor J. Dirita, Melody Neely, Ronald K. Taylor, Paul M. Bruss

Dartmouth Scholarship

The two major disease-causing biotypes of Vibrio cholerae, classical and El Tor, exhibit differences in their epidemic nature. Their behavior in the laboratory also differs in that El Tor strains produce two major virulence factors, cholera toxin (CT) and the toxin coregulated pilus (TCP), only under very restricted growth conditions, whereas classical strains do so in standard laboratory medium. Expression of toxin and TCP is controlled by two activator proteins, ToxR and ToxT, that operate in cascade fashion with ToxR controlling the synthesis of ToxT. Both biotypes express equivalent levels of ToxR, but only classical strains appear to express ToxT …


Genome Research And Traditional Intellectual Property Protection -- A Bad Fit?, Kate H. Murashige Jun 1996

Genome Research And Traditional Intellectual Property Protection -- A Bad Fit?, Kate H. Murashige

RISK: Health, Safety & Environment (1990-2002)

Dr. Murashige addresses the need for a patent system more closely tailored to the needs of biotechnology. For example, the obviousness requirement may interfere with using patents to recoup high costs of work when it could arguably be done by researchers of ordinary skill.


The Effect Of Acute Low Ph On Feeding And Locomotor Activity Of Larval Fathead Minnows, Pimephales Promelas, Sharon Ore May 1996

The Effect Of Acute Low Ph On Feeding And Locomotor Activity Of Larval Fathead Minnows, Pimephales Promelas, Sharon Ore

Masters Theses & Specialist Projects

Lowered pH conditions in aquatic environments can have a negative impact on many aquatic organisms. In fish it has been shown that acidic water conditions may result in altered gill morphology, reduced reproductive success, changes in locomotor and feeding behavior and even death. Juveniles and adults have been the primary focus of research. However, the larval stage is potentially the most sensitive to toxicity. It is also important ontogenetically as several crucial development thresholds, such as first feeding, occur during this period. The impact of acute low pH on feeding performance was investigated in larval fathead minnows one to fifteen …


Phenylbutyl Nitrone Compositions And Methods For Prevention Of Gastric Ulceration, John M. Carney, Robert A. Floyd Apr 1996

Phenylbutyl Nitrone Compositions And Methods For Prevention Of Gastric Ulceration, John M. Carney, Robert A. Floyd

Pharmacology and Nutritional Sciences Faculty Patents

Compositions containing PBN, or active derivatives thereof, in a suitable pharmaceutical carrier for administration to a patient, are disclosed for treating or preventing gastric ulceration caused by ingestion of non-steroidal anti-inflammatories. Based on animal studies, the dosage is in the range of 3 to 300 mg/kg and is administered prior to, simultaneously, or shortly after ingestion of the NSAID compounds(s). In the preferred embodiment, the range is between 10 and 30 mg/kg, depending on the dosage unit required to protect the mucosa. The preferred method of administration is orally, alone or in combination with the non-steroidal anti-inflammatory. It is believed …


2,4-Disulfonyl Phenyl Butyl Nitrone, Its Salt And Their Use As Pharmaceuticals, John M. Carney Apr 1996

2,4-Disulfonyl Phenyl Butyl Nitrone, Its Salt And Their Use As Pharmaceuticals, John M. Carney

Pharmacology and Nutritional Sciences Faculty Patents

2,4-disulfonyl α-phenyl-tert-butyl nitrone and its pharmaceutically acceptable salts are disclosed. These materials are useful as pharmaceutical agents for oral or parenteral, e.g. intravenous administration to patients suffering from acute central nervous system oxidation as occurs in a stroke or from gradual central nervous system oxidation which can exhibit itself as progressive central nervous system function loss. The materials are also used to ameliorate the side effects of oxidative-damage causing antineoplastic disease treatments.


Toxoplasma Gondii-Induced Immune Suppression By Human Peripheral Blood Monocytes: Role Of Gamma Interferon., Jacqueline Y. Channon, Lloyd H. Kasper Apr 1996

Toxoplasma Gondii-Induced Immune Suppression By Human Peripheral Blood Monocytes: Role Of Gamma Interferon., Jacqueline Y. Channon, Lloyd H. Kasper

Dartmouth Scholarship

The ability of Toxoplasma gondii to evade the host immune response during primary infection in humans is poorly understood. In murine toxoplasmosis, infected spleen macrophages release soluble factors that mediate a transient immunosuppression, which may allow the parasite to become established. When an enriched population of human monocytes from seronegative individuals was incubated with toxoplasmas in vitro, soluble factors that mediated market suppression of mitogen-induced lymphocyte DNA synthesis were released. Irradiated tachyzoites that do not undergo replication were sufficient stimuli for near-maximal soluble factor release. Up to 50% of the soluble factor-mediated suppression is attributable to a gamma interferon (IFN-gamma)-dependent …


Disruption Of The Cbfa2 Gene Causes Necrosis And Hemorrhaging In The Central Nervous System And Blocks Definitive Hematopoiesis., Qing Wang, Terryl Stacy, Michael M Binder, Miguel Marin-Padilla, Arlene H. Sharpe, Nancy A. Speck Apr 1996

Disruption Of The Cbfa2 Gene Causes Necrosis And Hemorrhaging In The Central Nervous System And Blocks Definitive Hematopoiesis., Qing Wang, Terryl Stacy, Michael M Binder, Miguel Marin-Padilla, Arlene H. Sharpe, Nancy A. Speck

Dartmouth Scholarship

The CBFA2 (AML1) gene encodes a DNA-binding subunit of the heterodimeric core-binding factor. The CBFA2 gene is disrupted by the (8;21), (3;21), and (12;21) chromosomal translocations associated with leukemias and myelodysplasias in humans. Mice lacking a CBF alpha 2 protein capable of binding DNA die between embryonic days 11.5 and 12.5 due to hemorrhaging in the central nervous system (CNS), at the nerve/CNS interfaces of cranial and spinal nerves, and in somitic/intersomitic regions along the presumptive spinal cord. Hemorrhaging is preceded by symmetric, bilateral necrosis in these regions. Definitive erythropoiesis and myelopoiesis do not occur in Cbfa2-deficient embryos, and disruption …


A Tandem Duplication Within The Fibrillin 1 Gene Is Associated With The Mouse Tight Skin Mutation., Linda D. Siracusa, Rodney Mcgrath, Qing Ma, John J. Moskow, Jayanthi Manne, Paul J. Christner, Arthur M. Buchberg, Sergio A. Jimenez Apr 1996

A Tandem Duplication Within The Fibrillin 1 Gene Is Associated With The Mouse Tight Skin Mutation., Linda D. Siracusa, Rodney Mcgrath, Qing Ma, John J. Moskow, Jayanthi Manne, Paul J. Christner, Arthur M. Buchberg, Sergio A. Jimenez

Department of Medicine Faculty Papers

Mice carrying the Tight skin (Tsk) mutation have thickened skin and visceral fibrosis resulting from an accumulation of extracellular matrix molecules. These and other connective tissue abnormalities have made Tskl + mice models for scleroderma, hereditary emphysema, and myocardial hypertrophy. Previously we localized Tsk to mouse chromosome 2 in a region syntenic with human chromosome 15. The microfibrillar glycoprotein gene, fibrillin 1 (FBN1), on human chromosome 15q, provided a candidate for the Tsk mutation. We now demonstrate that the Tsk chromosome harbors a 30- to 40-kb genomic duplication within the Fbn1 gene that results in a larger than normal in-frame …