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Amyloid neuropathology in the single Arctic APP transgenic model affects interconnected brain regions.

https://arctichealth.org/en/permalink/ahliterature131757
Source
Neurobiol Aging. 2012 Apr;33(4):831.e11-9
Publication Type
Article
Date
Apr-2012
Author
Annica Rönnbäck
Hanna Sagelius
Karin Dillner Bergstedt
Jan Näslund
Gunilla T Westermark
Bengt Winblad
Caroline Graff
Author Affiliation
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet Alzheimer Disease Research Center, Karolinska Institutet, Huddinge, Sweden. annica.ronnback@ki.se
Source
Neurobiol Aging. 2012 Apr;33(4):831.e11-9
Date
Apr-2012
Language
English
Publication Type
Article
Keywords
Age Factors
Alzheimer Disease - genetics - metabolism - pathology
Amyloid beta-Peptides - metabolism
Amyloid beta-Protein Precursor - genetics - metabolism
Analysis of Variance
Animals
Disease Models, Animal
Enzyme-Linked Immunosorbent Assay - methods
Female
Hippocampus - metabolism - pathology - ultrastructure
Humans
Male
Mice
Mice, Transgenic
Microscopy, Immunoelectron
Mutation - genetics
Peptide Fragments - metabolism
Abstract
The Arctic APP mutation (E693G) within the amyloid ß (Aß) domain of amyloid precursor protein (APP) leads to dementia with clinical features similar to Alzheimer's disease (AD), which is believed to be mediated via increased formation of protofibrils. We have generated a transgenic mouse model, TgAPParc, with neuron-specific expression of human amyloid precursor protein with the Arctic mutation (hAPParc), showing mild amyloid pathology with a relatively late onset. Here we performed a detailed analysis of the spatiotemporal progression of neuropathology in homozygous TgAPParc, focusing on intracellular Aß and diffuse Aß aggregates rather than amyloid plaques. We show that the neuropathology in homozygous TgAPParc mice starts with intracellular Aß aggregates, which is followed by diffuse extracellular Aß deposits in subiculum that later expands to brain regions receiving neuronal projections from regions already affected. Together this suggests that the pathology in TgAPParc mice affects interconnected brain regions and may represent a valuable tool to study the spread and progression of neuropathology in Alzheimer's disease.
PubMed ID
21880397 View in PubMed
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Bile canaliculus formation in cultured HEPG2 cells.

https://arctichealth.org/en/permalink/ahliterature24022
Source
Lab Invest. 1993 Jun;68(6):652-62
Publication Type
Article
Date
Jun-1993
Author
R. Sormunen
S. Eskelinen
V P Lehto
Author Affiliation
Biocenter, University of Oulu, Finland.
Source
Lab Invest. 1993 Jun;68(6):652-62
Date
Jun-1993
Language
English
Publication Type
Article
Keywords
Bile Canaliculi - chemistry - growth & development - ultrastructure
Carcinoma, Hepatocellular - chemistry - ultrastructure
Humans
Liver Neoplasms - chemistry - ultrastructure
Microfilament Proteins - analysis
Microscopy, Electron
Microscopy, Immunoelectron
Research Support, Non-U.S. Gov't
Tumor Cells, Cultured
Abstract
BACKGROUND: The plasma membrane of hepatocytes can be divided in sinusoidal, lateral and apical membrane, each with functionally and structurally distinct features. The apical domain consists of the bile canalicular structures. The morphogenesis and the polarization of hepatocytes is still poorly known. EXPERIMENTAL DESIGN: We used HepG2 cells, a hepatoma cell line to study the formation of the bile canaliculi in the apical part of the cells. The cells were synchronized by using nocodazole. The formation of the bile canaliculi was monitored by using immunofluorescence microscopy, confocal laser scanning microscopy, and immunoelectron microscopy. Antibodies to alpha-fodrin and villin were used. Actin was visualized with rhodamine phalloidin. RESULTS: Confocal laser scanning microscopy showed accumulations of actin, villin and fodrin at the cell membranes 8 to 12 hours after the release of the nocodazole block. These sites probably represent areas destined to develop into bile canaliculi. Later, immature bile canaliculi were discerned that were located asymmetrically between adjacent cells. Transmission electron microscopy of serial sections showed that they were always connected with the surface of the cell. Mature bile canaliculi appeared between adjacent cells 48 hours after the release of the nocodazole block. They were round, vesicle-like structures lined with microvilli and sealed by tight junctions and desmosomes. They were usually seen between two juxtaposed cells, and often several cells contributed to their formation. Typically, mature bile canaliculi were delineated by a subplasmalemmal filamentous meshwork of fodrin and actin, resembling a terminal web of enterocytes. Actin and villin were also found in microvillar cores. CONCLUSIONS: The results show that (i) bile canaliculi are formed de novo between two or more juxtaposed cells; (ii) canalicular-formation is accompanied by a distinct accumulation of the membrane skeletal and microvillar proteins fodrin, actin and villin at the apical surfaces of the cells, suggesting that they play an important role in bile canaliculus morphogenesis, and that (iii) apical membrane differentiation in the cells contributing to the formation of a single canaliculus is an asymmetric process.
PubMed ID
8390592 View in PubMed
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Detection of latex allergens by immunoelectron microscopy in ambient air (PM10) in Oslo, Norway (1997-2003).

https://arctichealth.org/en/permalink/ahliterature177335
Source
J Environ Health. 2004 Nov;67(4):20-6, 28
Publication Type
Article
Date
Nov-2004
Author
Ellen Namork
Viswanath P Kurup
Gunn Marit Aasvang
Bjørn V Johansen
Author Affiliation
Department of Enviromental Immunology, Noregian Institute of Public Health, Oslo. ellen.namork@fhi.no
Source
J Environ Health. 2004 Nov;67(4):20-6, 28
Date
Nov-2004
Language
English
Publication Type
Article
Keywords
Air Pollutants - analysis
Allergens - analysis
Automobile Driving
Environmental Monitoring - methods
Humans
Latex - immunology
Latex Hypersensitivity - etiology
Microscopy, Immunoelectron - methods
Norway
Particle Size
Seasons
Abstract
The authors collected ambient air along two highways in Oslo to investigate the annual variations in particulate matter (PM10) and the presence of latex as an outdoor allergen. PMI, was monitored for a period of five years, during which time the use of studded winter tires was reduced. The presence of latex and of common aeroallergens was examined directly on the collection filters with immunoelectron microscopy visualized in a scanning electron microscope. The annual variation in PM10 was similar over the five years of sampling, with increased mass concentrations in winter. Statistical analysis indicated no major effect from the change to nonstudded tires. The most important factors influencing the PM10 concentration were meteorological parameters like wind and rain. Immnunolabeling of the filters showed latex as an outdoor allergen that adhered to carbon aggregates from vehicle emission. The results also indicated cross-reactive epitopes among the common allergens investigated, which for sensitized subjects may add to the risk of developing latex allergy.
PubMed ID
15552702 View in PubMed
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Distribution of tetrodotoxin in the ribbon worm Lineus alborostratus (Takakura, 1898) (nemertea): Immunoelectron and immunofluorescence studies.

https://arctichealth.org/en/permalink/ahliterature278367
Source
Toxicon. 2016 Mar 15;112:29-34
Publication Type
Article
Date
Mar-15-2016
Author
Timur Yu Magarlamov
Olga A Shokur
Alexey V Chernyshev
Source
Toxicon. 2016 Mar 15;112:29-34
Date
Mar-15-2016
Language
English
Publication Type
Article
Keywords
Animals
Aquatic Organisms - growth & development - metabolism - ultrastructure
Endoplasmic Reticulum - metabolism - ultrastructure
Invertebrates - growth & development - metabolism - ultrastructure
Microscopy, Confocal - veterinary
Microscopy, Electron, Transmission - veterinary
Microscopy, Fluorescence - veterinary
Microscopy, Immunoelectron - veterinary
Neurotoxins - metabolism - toxicity
Nuclear Envelope - metabolism - ultrastructure
Pacific Ocean
Russia
Secretory Vesicles - metabolism - ultrastructure
Sodium Channel Blockers - metabolism - toxicity
Tetrodotoxin - metabolism - toxicity
Tissue Distribution
Toxicokinetics
Abstract
Transmission electron and confocal laser scanning (CLSM) microscopies with monoclonal anti-tetrodotoxin antibodies were used to locate tetrodotoxin (TTX) in tissues and gland cells of the ribbon worm Lineus alborostratus. CLSM studies have shown that the toxin is primarily localized in the cutis (special subepidermal layer) of the body wall and in the glandular epithelium of the proboscis. Immunoelectron micrographs have shown that only subepidermal bacillary gland cells type I in cutis and pseudocnidae-containing and mucoid gland cells manifested TTX-gold labeling. TTX was associated with the nuclear envelope, endoplasmic reticulum membrane, and secretory granules of TTX-positive gland cells. These studies indicate that ??? is brought into the cytoplasm of the glandular cells of the cutis and proboscis epithelium, where it is associated with membrane-enclosed organelles involved in protein secretion and then concentrated in glandular granules.
PubMed ID
26821373 View in PubMed
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Endostatin overexpression specifically in the lens and skin leads to cataract and ultrastructural alterations in basement membranes.

https://arctichealth.org/en/permalink/ahliterature50596
Source
Am J Pathol. 2005 Jan;166(1):221-9
Publication Type
Article
Date
Jan-2005
Author
Harri Elamaa
Raija Sormunen
Marko Rehn
Raija Soininen
Taina Pihlajaniemi
Author Affiliation
Department of Medical Biochemistry and Molecular Biology, Biocenter Oulu, University of Oulu, Aapistie 7, FI 90220, Oulu, Finland.
Source
Am J Pathol. 2005 Jan;166(1):221-9
Date
Jan-2005
Language
English
Publication Type
Article
Keywords
Angiogenesis Inhibitors
Animals
Basement Membrane - pathology - ultrastructure
Cataract - pathology
DNA Primers
Endostatins - physiology
Humans
Lens, Crystalline - pathology - ultrastructure
Mice
Mice, Transgenic
Microscopy, Immunoelectron
Polymerase Chain Reaction
Research Support, Non-U.S. Gov't
Skin - pathology - ultrastructure
Abstract
Endostatin, a proteolytic fragment of type XVIII collagen, has been shown to inhibit angiogenesis, tumor growth, and endothelial cell proliferation and migration. We analyzed its functions in vivo by generating transgenic mice in which it was overexpressed in the skin and lens capsule under the keratin K14 promoter. Opacity of the lens occurred at 4 months of age in the mouse line J4, with the highest level of endostatin expression. The lens epithelial cells appeared to lose contact with the capsule and began to vacuolize. In 1-year-old mice the lens epithelial cell layer had entirely degenerated, and instead, large plaques of spindle-shaped cells had formed in the anterior region of the lens. Moreover, a widening of the epidermal basement membrane (BM) zone of the skin was observed in electron microscopy. The epidermal BM was conspicuously altered in the J4 mice with high transgene expression, including clear broadening and occurrence of pearl-like protrusions in some areas, whereas the BM was more even in appearance but consistently broadened in the mouse line G20 with moderate transgene expression. In both lines the BM was continuous. Measurements indicated that the lamina densa was 78.54 +/- 53.10 nm in line J4, the large variation reflecting the protrusions of the lamina densa, and 44.24 +/- 11.52 nm in line G20, compared with 33.74 +/- 9.96 nm in wild-type adult mice. Immunoelectron microscopy of wild-type mouse skin type XVIII collagen showed a polarized orientation in the BMs, with the C-terminal endostatin region localized in the lamina densa and the N terminus in average approximately 40 nm more on the dermal side. Type XVIII collagen was dispersed in the transgenic skin, suggesting that the transgene-derived endostatin fragment displaces the full-length collagen XVIII. This may impair the anchoring of the lamina densa to the dermis and thereby lead to loosening of the BMs, resembling the previously observed situation in collagen XVIII-null mice.
PubMed ID
15632014 View in PubMed
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Expression and prognostic significance of catalase in malignant mesothelioma.

https://arctichealth.org/en/permalink/ahliterature19913
Source
Cancer. 2001 Apr 1;91(7):1349-57
Publication Type
Article
Date
Apr-1-2001
Author
K. Kahlos
Y. Soini
R. Sormunen
R. Kaarteenaho-Wiik
P. Pääkkö
K. Linnainmaa
V L Kinnula
Author Affiliation
Department of Internal Medicine, University of Oulu, FIN-90220, Oulu, Finland.
Source
Cancer. 2001 Apr 1;91(7):1349-57
Date
Apr-1-2001
Language
English
Publication Type
Article
Keywords
Amitrole - pharmacology
Blotting, Western
Catalase - metabolism
Epirubicin - pharmacology
Humans
Immunohistochemistry
Mesothelioma - enzymology - mortality
Microscopy, Immunoelectron
Pleural Neoplasms - enzymology - mortality
Prognosis
Research Support, Non-U.S. Gov't
Superoxide Dismutase - metabolism
Survival Rate
Tumor Cells, Cultured
Tumor Markers, Biological - analysis
Abstract
BACKGROUND: Free radicals and antioxidant enzymes (AOEs) may play a critical role in cell proliferation and in the resistance of malignant cells against cytotoxic drugs and radiation. Malignant mesothelioma is a resistant tumor with high levels of manganese superoxide dismutase, a central superoxide scavenging AOE. In the current study, the authors assessed the expression and prognostic role of catalase, an important hydrogen peroxide scavenging AOE, in malignant pleural mesothelioma. METHODS: Catalase expression was investigated by immunohistochemistry in 5 cases of nonmalignant healthy pleura and in tumor tissue of 32 mesothelioma patients, and by Western blot in 7 continuous human mesothelioma cell lines. The distribution of catalase in mesothelioma cells was assessed by immunoelectron microscopy. Furthermore, to investigate the effect of catalase inhibition in the drug resistance of these cells in vitro, the authors exposed mesothelioma cells with the highest catalase level to epirubicin with and without aminotriazole pretreatment. RESULTS: Nonmalignant mesothelial cells showed no catalase immunoreactivity whereas most mesothelioma cases (24 of 32, 75%) were catalase positive, 17 cases (53%) showing moderate or high expression. Higher catalase expression in mesothelioma was associated with a better prognosis, mean survival rate from diagnosis being 6 and 24 months for negative/low expression and moderate/high expression, respectively. Furthermore, a coordinately high expression of both manganese-superoxide dismutase (Mn-SOD) and catalase predicted even more favorable outcome of the mesothelioma patients. Catalase also could be detected in all mesothelioma cell lines, the most resistant cell line showing the highest protein expression and compartmentalization of catalase mainly to peroxisomes. Aminotriazole inhibition of catalase had a marginal effect on the toxicity caused by epirubicin. CONCLUSIONS: Catalase may have multifactorial effects in malignant cells; high catalase and/or coordinated high expression of Mn-SOD and catalase may decrease tumor progression by modulating the cellular redox state, but enhanced antioxidant capacity of mesothelioma cells also may protect tumor cells against exogenous oxidants, at least in vitro.
PubMed ID
11283936 View in PubMed
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Fodrin and actin in the normal, metaplastic, and dysplastic respiratory epithelium and in lung carcinoma.

https://arctichealth.org/en/permalink/ahliterature23608
Source
Am J Respir Cell Mol Biol. 1994 Jul;11(1):75-84
Publication Type
Article
Date
Jul-1994
Author
R. Sormunen
P. Pääkkö
R. Palovuori
Y. Soini
V P Lehto
Author Affiliation
Biocenter, University of Oulu, Finland.
Source
Am J Respir Cell Mol Biol. 1994 Jul;11(1):75-84
Date
Jul-1994
Language
English
Publication Type
Article
Keywords
Actins - analysis
Animals
Antibodies, Monoclonal
Bronchi - chemistry
Carrier Proteins - analysis
Chickens
Epithelium - chemistry - pathology
Fluorescent Antibody Technique
Humans
Immunoblotting
Lung Neoplasms - chemistry - pathology
Microfilament Proteins - analysis
Microscopy, Fluorescence
Microscopy, Immunoelectron
Pulmonary Alveoli - chemistry
Research Support, Non-U.S. Gov't
Tissue Distribution
Abstract
Distribution of actin and fodrin, a nonerythroid analogue of spectrin, was studied in cytocentrifuge preparations and in tissue sections of normal and pathologic respiratory epithelium by using immunofluorescence and immunoelectron microscopy. In ciliated epithelial cells and in goblet cells of normal bronchial epithelium, fodrin and actin were located in the apical parts and along the lateral walls of the cells. In basal cells, fodrin and actin were also seen diffusely in the cytoplasm. Immunoelectron microscopy showed fodrin in close association with the basal bodies and rootlets of the cilia and microvilli in the ciliated cells. In alveolar epithelium, fodrin and actin were located at the apical membrane in type I pneumocytes and along the apical and lateral membranes in type II pneumocytes. In type II pneumocytes, fodrin was also seen in close association with the secretory vacuoles. In metaplastic and dysplastic bronchial epithelium, a diffuse cytoplasmic and a circumferential, membrane-associated staining for fodrin and actin was seen. In all types of carcinomas, fodrin was seen along the lateral walls and diffusely in the cytoplasm. The staining was more intense than in the normal cells. In immunoblotting of the normal bronchial epithelium, and peripheral lung and lung carcinomas, a single 240 kD band was recognized with antibodies to fodrin. The results show distinct differences in the distribution of fodrin in the various cell types of the respiratory epithelium. In ciliated cells, the close relationship with cytoskeleton suggests a role of fodrin in the establishment of the elaborate structural architecture of the apical compartment. In type II pneumocytes, on the other hand, fodrin probably plays a role in secretion of the surfactant. In basal cells, the diffuse distribution of fodrin probably reflects the high proliferative capacity of this cell compartment. Interestingly, a similar distribution was also seen in premalignant and malignant cells.
PubMed ID
8018340 View in PubMed
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Immuno-electron-microscopic localization of types III pN-collagen and IV collagen, laminin and tenascin in developing and adult human spleen.

https://arctichealth.org/en/permalink/ahliterature59258
Source
Cell Tissue Res. 1995 Oct;282(1):117-27
Publication Type
Article
Date
Oct-1995
Author
A. Liakka
H. Karjalainen
I. Virtanen
H. Autio-Harmainen
Author Affiliation
Department of Pathology, University of Oulu, Kajaanintie 52 D, SF-90220 Oulu, Finland.
Source
Cell Tissue Res. 1995 Oct;282(1):117-27
Date
Oct-1995
Language
English
Publication Type
Article
Keywords
Adult
Aged
Collagen - analysis
Embryonic and Fetal Development - physiology
Extracellular Matrix Proteins - analysis
Humans
Infant, Newborn
Laminin - analysis
Microscopy, Immunoelectron
Peptide Fragments - analysis
Procollagen - analysis
Research Support, Non-U.S. Gov't
Spleen - chemistry - embryology - growth & development
Tenascin - analysis
Abstract
The distribution of the extracellular matrix proteins types III pN-collagen and IV collagen, laminin and tenascin was investigated in fetal, infant, and adult human spleens by using immuno-electron microscopy. The presence of type III pN-collagen was assessed by using an antibody against the aminoterminal propeptide of type III procollagen. All the proteins other than type III pN-collagen were found in reticular fibers throughout development. In the white pulp of the fetus aged 16 gestational weeks, only an occasional type III pN-collagen-containing fibril was present, although type III pN-collagen was abundant in the reticular fibers of the red pulp. Conversely, in adults, most of the reticular fibers of the white pulp, but not of the red pulp, were immunoreactive for type III pN-collagen. Ring fibers, the basement membranes of venous sinuses, were well developed in both infant and adult spleens. The first signs of their formation could be seen as a discontinuous basement membrane, which was immunoreactive for type IV collagen, laminin, and tenascin in the fetus aged 20 gestational weeks. Intracytoplasmic immunoreactivity for all the proteins studied was visible in the mesenchymal cells of the fetus aged 16 gestational weeks and in the reticular cells of the older fetuses, which also showed labeling for type IV collagen and laminin in the endothelial cells. The results suggest that proteins of the extracellular matrix are produced by these stationary cells.
PubMed ID
8581914 View in PubMed
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Lack of collagen XV impairs peripheral nerve maturation and, when combined with laminin-411 deficiency, leads to basement membrane abnormalities and sensorimotor dysfunction.

https://arctichealth.org/en/permalink/ahliterature100185
Source
J Neurosci. 2010 Oct 27;30(43):14490-501
Publication Type
Article
Date
Oct-27-2010
Author
Karolina Rasi
Merja Hurskainen
Mika Kallio
Saara Stavén
Raija Sormunen
Anthony M Heape
Robin L Avila
Daniel Kirschner
Anu Muona
Uolevi Tolonen
Heikki Tanila
Pirkko Huhtala
Raija Soininen
Taina Pihlajaniemi
Author Affiliation
Oulu Center for Cell-Matrix Research, Biocenter Oulu, Department of Medical Biochemistry and Molecular Biology, University of Oulu, and Department of Clinical Neurophysiology, Oulu University Hospital, FIN-90221 Oulu, Finland.
Source
J Neurosci. 2010 Oct 27;30(43):14490-501
Date
Oct-27-2010
Language
English
Publication Type
Article
Keywords
Action Potentials - physiology
Animals
Axons - physiology - ultrastructure
Basement Membrane - physiology - ultrastructure
Behavior, Animal - physiology
Collagen - genetics - physiology
Electrophysiology
Enzyme-Linked Immunosorbent Assay
Laminin - genetics - physiology
Male
Mice
Mice, Knockout
Microscopy, Immunoelectron
Motor Neurons - physiology
Myelin Sheath - physiology
Nerve Fibers, Unmyelinated - physiology
Neural Conduction - physiology
Peripheral Nerves - physiology - ultrastructure
Physical Stimulation
Reflex - physiology
Sensory Receptor Cells - physiology
Sensory Thresholds - physiology
Somatosensory Disorders - genetics - physiopathology
X-Ray Diffraction
Abstract
Although the Schwann cell basement membrane (BM) is required for normal Schwann cell terminal differentiation, the role of BM-associated collagens in peripheral nerve maturation is poorly understood. Collagen XV is a BM zone component strongly expressed in peripheral nerves, and we show that its absence in mice leads to loosely packed axons in C-fibers and polyaxonal myelination. The simultaneous lack of collagen XV and another peripheral nerve component affecting myelination, laminin a4, leads to severely impaired radial sorting and myelination, and the maturation of the nerve is permanently compromised, contrasting with the slow repair observed in Lama4-/- single knock-out mice. Moreover, the Col15a1-/-;Lama4-/- double knock-out (DKO) mice initially lack C-fibers and, even over 1 year of age have only a few, abnormal C-fibers. The Lama4-/- knock-out results in motor and tactile sensory impairment, which is exacerbated by a simultaneous Col15a1-/- knock-out, whereas sensitivity to heat-induced pain is increased in the DKO mice. Lack of collagen XV results in slower sensory nerve conduction, whereas the Lama4-/- and DKO mice exhibit increased sensory nerve action potentials and decreased compound muscle action potentials; x-ray diffraction revealed less mature myelin in the sciatic nerves of the latter than in controls. Ultrastructural analyses revealed changes in the Schwann cell BM in all three mutants, ranging from severe (DKO) to nearly normal (Col15a1-/-). Collagen XV thus contributes to peripheral nerve maturation and C-fiber formation, and its simultaneous deletion from neural BM zones with laminin a4 leads to a DKO phenotype distinct from those of both single knock-outs.
PubMed ID
20980607 View in PubMed
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Lack of cytosolic and transmembrane domains of type XIII collagen results in progressive myopathy.

https://arctichealth.org/en/permalink/ahliterature49856
Source
Am J Pathol. 2001 Oct;159(4):1581-92
Publication Type
Article
Date
Oct-2001
Author
A P Kvist
A. Latvanlehto
M. Sund
L. Eklund
T. Väisänen
P. Hägg
R. Sormunen
J. Komulainen
R. Fässler
T. Pihlajaniemi
Author Affiliation
Department of Medical Biochemistry, Biocenter Oulu, University of Oulu, Oulu, Finland.
Source
Am J Pathol. 2001 Oct;159(4):1581-92
Date
Oct-2001
Language
English
Publication Type
Article
Keywords
Amino Acid Sequence - genetics
Animals
Cell Adhesion - physiology
Cell Membrane - metabolism
Cells, Cultured
Collagen Type XIII - chemistry - genetics - metabolism
Cytosol - metabolism
Disease Progression
Exons
Fibroblasts - physiology
Gene Deletion
Mice
Mice, Transgenic
Microscopy, Immunoelectron
Molecular Sequence Data
Motor Activity
Muscle, Skeletal - pathology - ultrastructure
Muscular Diseases - etiology - pathology - physiopathology
Protein Structure, Tertiary
Recombination, Genetic
Research Support, Non-U.S. Gov't
Abstract
Type XIII collagen is a type II transmembrane protein found at many sites of cell adhesion in tissues. Homologous recombination was used to generate a transgenic mouse line (Col13a1(N/N)) that expresses N-terminally altered type XIII collagen molecules lacking the short cytosolic and transmembrane domains but retaining the large collagenous ectodomain. The mutant molecules were correctly transported to focal adhesions in cultured fibroblasts derived from the Col13a1(N/N) mice, but the cells showed decreased adhesion when plated on type IV collagen. These mice were viable and fertile, and in immunofluorescence stainings the mutant protein was located in adhesive tissue structures in the same manner as normal alpha1(XIII) chains. In immunoelectron microscopy of wild-type mice type XIII collagen was detected at the plasma membrane of skeletal muscle cells whereas in the mutant mice the protein was located in the adjacent extracellular matrix. Affected skeletal muscles showed abnormal myofibers with a fuzzy plasma membrane-basement membrane interphase along the muscle fiber and at the myotendinous junctions, disorganized myofilaments, and streaming of z-disks. The findings were progressive and the phenotype was aggravated by exercise. Thus type XIII collagen seems to participate in the linkage between muscle fiber and basement membrane, a function impaired by lack of the cytosolic and transmembrane domains.
PubMed ID
11583983 View in PubMed
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16 records – page 1 of 2.