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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en"><italic>Emilin1</italic> Deficiency Causes Structural and Functional Defects of Lymphatic Vasculature <xref ref-type="fn" rid="fn1">▿</xref> </title><author><name sortKey="Danussi, Carla" sort="Danussi, Carla" uniqKey="Danussi C" first="Carla" last="Danussi">Carla Danussi</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Spessotto, Paola" sort="Spessotto, Paola" uniqKey="Spessotto P" first="Paola" last="Spessotto">Paola Spessotto</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Petrucco, Alessandra" sort="Petrucco, Alessandra" uniqKey="Petrucco A" first="Alessandra" last="Petrucco">Alessandra Petrucco</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wassermann, Bruna" sort="Wassermann, Bruna" uniqKey="Wassermann B" first="Bruna" last="Wassermann">Bruna Wassermann</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Sabatelli, Patrizia" sort="Sabatelli, Patrizia" uniqKey="Sabatelli P" first="Patrizia" last="Sabatelli">Patrizia Sabatelli</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Montesi, Monica" sort="Montesi, Monica" uniqKey="Montesi M" first="Monica" last="Montesi">Monica Montesi</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Doliana, Roberto" sort="Doliana, Roberto" uniqKey="Doliana R" first="Roberto" last="Doliana">Roberto Doliana</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Bressan, Giorgio M" sort="Bressan, Giorgio M" uniqKey="Bressan G" first="Giorgio M." last="Bressan">Giorgio M. Bressan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Colombatti, Alfonso" sort="Colombatti, Alfonso" uniqKey="Colombatti A" first="Alfonso" last="Colombatti">Alfonso Colombatti</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">18411305</idno><idno type="pmc">2423131</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2423131</idno><idno type="RBID">PMC:2423131</idno><idno type="doi">10.1128/MCB.02062-07</idno><date when="2008">2008</date><idno type="wicri:Area/Pmc/Corpus">001959</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">001959</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main"><italic>Emilin1</italic> Deficiency Causes Structural and Functional Defects of Lymphatic Vasculature <xref ref-type="fn" rid="fn1">▿</xref> </title><author><name sortKey="Danussi, Carla" sort="Danussi, Carla" uniqKey="Danussi C" first="Carla" last="Danussi">Carla Danussi</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Spessotto, Paola" sort="Spessotto, Paola" uniqKey="Spessotto P" first="Paola" last="Spessotto">Paola Spessotto</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Petrucco, Alessandra" sort="Petrucco, Alessandra" uniqKey="Petrucco A" first="Alessandra" last="Petrucco">Alessandra Petrucco</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Wassermann, Bruna" sort="Wassermann, Bruna" uniqKey="Wassermann B" first="Bruna" last="Wassermann">Bruna Wassermann</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Sabatelli, Patrizia" sort="Sabatelli, Patrizia" uniqKey="Sabatelli P" first="Patrizia" last="Sabatelli">Patrizia Sabatelli</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Montesi, Monica" sort="Montesi, Monica" uniqKey="Montesi M" first="Monica" last="Montesi">Monica Montesi</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Doliana, Roberto" sort="Doliana, Roberto" uniqKey="Doliana R" first="Roberto" last="Doliana">Roberto Doliana</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Bressan, Giorgio M" sort="Bressan, Giorgio M" uniqKey="Bressan G" first="Giorgio M." last="Bressan">Giorgio M. Bressan</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author><author><name sortKey="Colombatti, Alfonso" sort="Colombatti, Alfonso" uniqKey="Colombatti A" first="Alfonso" last="Colombatti">Alfonso Colombatti</name><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation><affiliation><nlm:aff id="aff1"></nlm:aff></affiliation></author></analytic><series><title level="j">Molecular and Cellular Biology</title><idno type="ISSN">0270-7306</idno><idno type="eISSN">1098-5549</idno><imprint><date when="2008">2008</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Lymphatic-vasculature function critically depends on extracellular matrix (ECM) and on its connections with lymphatic endothelial cells (LECs). However, the composition and the architecture of ECM have not been fully taken into consideration in studying the biology and the pathology of the lymphatic system. EMILIN1, an elastic microfibril-associated protein, is highly expressed by LECs in vitro and colocalizes with lymphatic vessels in several mouse tissues. A comparative study between WT and <italic>Emilin1</italic><sup>−/−</sup> mice highlighted the fact that <italic>Emilin1</italic> deficiency in both CD1 and C57BL/6 backgrounds results in hyperplasia, enlargement, and frequently an irregular pattern of superficial and visceral lymphatic vessels and in a significant reduction of anchoring filaments. <italic>Emilin1</italic>-deficient mice also develop larger lymphangiomas than WT mice. Lymphatic vascular morphological alterations are accompanied by functional defects, such as mild lymphedema, a highly significant drop in lymph drainage, and enhanced lymph leakage. Our findings demonstrate that EMILIN1 is involved in the regulation of the growth and in the maintenance of the integrity of lymphatic vessels, a fundamental requirement for efficient function. The phenotype displayed by <italic>Emilin1</italic><sup>−/−</sup> mice is the first abnormal lymphatic phenotype associated with the deficiency of an ECM protein and identifies EMILIN1 as a novel local regulator of lymphangiogenesis.</p></div></front></TEI><pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">Mol Cell Biol</journal-id><journal-id journal-id-type="publisher-id">mcb</journal-id><journal-title>Molecular and Cellular Biology</journal-title><issn pub-type="ppub">0270-7306</issn><issn pub-type="epub">1098-5549</issn><publisher><publisher-name>American Society for Microbiology (ASM)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">18411305</article-id><article-id pub-id-type="pmc">2423131</article-id><article-id pub-id-type="publisher-id">2062-07</article-id><article-id pub-id-type="doi">10.1128/MCB.02062-07</article-id><article-categories><subj-group subj-group-type="heading"><subject>Articles</subject></subj-group></article-categories><title-group><article-title><italic>Emilin1</italic> Deficiency Causes Structural and Functional Defects of Lymphatic Vasculature <xref ref-type="fn" rid="fn1">▿</xref> </article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Danussi</surname><given-names>Carla</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Spessotto</surname><given-names>Paola</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Petrucco</surname><given-names>Alessandra</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Wassermann</surname><given-names>Bruna</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Sabatelli</surname><given-names>Patrizia</given-names></name><xref ref-type="aff" rid="aff1">2</xref></contrib><contrib contrib-type="author"><name><surname>Montesi</surname><given-names>Monica</given-names></name><xref ref-type="aff" rid="aff1">3</xref></contrib><contrib contrib-type="author"><name><surname>Doliana</surname><given-names>Roberto</given-names></name><xref ref-type="aff" rid="aff1">1</xref></contrib><contrib contrib-type="author"><name><surname>Bressan</surname><given-names>Giorgio M.</given-names></name><xref ref-type="aff" rid="aff1">3</xref></contrib><contrib contrib-type="author"><name><surname>Colombatti</surname><given-names>Alfonso</given-names></name><xref ref-type="aff" rid="aff1">1</xref><xref ref-type="aff" rid="aff1">4</xref><xref ref-type="aff" rid="aff1">5</xref><xref ref-type="corresp" rid="cor1">*</xref></contrib></contrib-group><aff id="aff1">Division of Experimental Oncology 2, Department of Molecular Oncology and Translational Research, CRO-IRCCS, Aviano, Pordenone, Italy,<label>1</label> IGM-CNR, Unit of Bologna c/o IOR, Bologna, Italy,<label>2</label> Mouse Genetics Laboratory, Department of Histology Microbiology and Medical Biotechnologies, University of Padua, Padua, Italy,<label>3</label> Department of Biomedical Sciences and Technologies, University of Udine, Udine, Italy,<label>4</label> MATI Center of Excellence, University of Udine, Udine, Italy<label>5</label></aff><author-notes><fn id="cor1"><label>*</label><p>Corresponding author. Mailing address: Division of Experimental Oncology 2, Department of Molecular Oncology and Translational Research, CRO-IRCCS, via F. Gallini 2, 33081 Aviano, Pordenone, Italy. Phone: 39 0434 659 365. Fax: 39 0434 659 428. E-mail: <email>acolombatti@cro.it</email></p></fn></author-notes><pub-date pub-type="ppub"><month>6</month><year>2008</year></pub-date><pub-date pub-type="epub"><day>14</day><month>4</month><year>2008</year></pub-date><volume>28</volume><issue>12</issue><fpage>4026</fpage><lpage>4039</lpage><history><date date-type="received"><day>16</day><month>11</month><year>2007</year></date><date date-type="rev-recd"><day>25</day><month>12</month><year>2007</year></date><date date-type="accepted"><day>27</day><month>3</month><year>2008</year></date></history><permissions><copyright-statement>Copyright © 2008, American Society for Microbiology</copyright-statement></permissions><self-uri xlink:title="pdf" xlink:href="zmb01208004026.pdf"></self-uri><abstract><p>Lymphatic-vasculature function critically depends on extracellular matrix (ECM) and on its connections with lymphatic endothelial cells (LECs). However, the composition and the architecture of ECM have not been fully taken into consideration in studying the biology and the pathology of the lymphatic system. EMILIN1, an elastic microfibril-associated protein, is highly expressed by LECs in vitro and colocalizes with lymphatic vessels in several mouse tissues. A comparative study between WT and <italic>Emilin1</italic><sup>−/−</sup> mice highlighted the fact that <italic>Emilin1</italic> deficiency in both CD1 and C57BL/6 backgrounds results in hyperplasia, enlargement, and frequently an irregular pattern of superficial and visceral lymphatic vessels and in a significant reduction of anchoring filaments. <italic>Emilin1</italic>-deficient mice also develop larger lymphangiomas than WT mice. Lymphatic vascular morphological alterations are accompanied by functional defects, such as mild lymphedema, a highly significant drop in lymph drainage, and enhanced lymph leakage. Our findings demonstrate that EMILIN1 is involved in the regulation of the growth and in the maintenance of the integrity of lymphatic vessels, a fundamental requirement for efficient function. The phenotype displayed by <italic>Emilin1</italic><sup>−/−</sup> mice is the first abnormal lymphatic phenotype associated with the deficiency of an ECM protein and identifies EMILIN1 as a novel local regulator of lymphangiogenesis.</p></abstract></article-meta></front><floats-wrap><fig position="float" id="f1"><label>FIG. 1.</label><caption><p>Human and mouse LECs express high levels of EMILIN1 in vitro. (A) Characterization of human lung and dermal neonatal LECs (HMVEC-LLy and HMVEC-dLyNeo). The positive staining for the lymphatic specific markers, LYVE-1, Prox-1, VEGFR-3, podoplanin, and CD31, is green. Nuclei were stained by ToPro (blue). Scale bar, 45 μm. (B) Quantitative RT-PCR was performed on mRNA extracted from LECs (HMVEC-LLy and HMVEC-dLyNeo, at passage 5) and blood endothelial cells (HUVEC, at passage 4). The relative EMILIN1 (E1) expression versus β-actin was quantified using the SDS 2.1 program. The analysis confirmed abundant EMILIN1 expression by LECs, revealing a threefold increase in HMVEC-LLy (**, <italic>P</italic> < 6 × 10<sup>−6</sup>) and a twofold increase in HMVEC-dLyNeo (*, <italic>P</italic> < 0.006) compared with HUVEC. HMVEC-LLy produced higher levels of EMILIN1 then did HMVEC-dLyNeo (‡, <italic>P</italic> < 0.006). (C) Comparative RT-PCR analysis of EMILIN1 mRNA levels in mouse LAECs and in bEnd3 (a mouse endothelioma cell line). (D) Immunofluorescence staining of EMILIN1 (green) shows its abundant production and extracellular deposition by LAECs (left) compared to bEnd3 cells (right). Nuclei were stained red by propidium iodide. Scale bar, 10 μm.</p></caption><graphic xlink:href="zmb0120875460001"></graphic></fig><fig position="float" id="f2"><label>FIG. 2.</label><caption><p>EMILIN1 is expressed in association with lymphatic vessels. (A to D) Cryostat sections of normal mouse tissues doubly stained with anti-EMILIN1 (green) and anti-LYVE-1 (red) antibodies. In all mouse tissues and organs examined, EMILIN1 was uniformly distributed in the stroma. (A) In the skin, EMILIN1 staining colocalizes with LYVE-1-positive lymphatic vessels surrounding hair follicles (arrowheads; scale bar, 75 μm). (B) In the small intestine, EMILIN1 colocalizes with LYVE-1-positive lacteals and submucosal lymphatic vessels (arrowheads; scale bar, 75 μm). (C and D) At higher magnification, in the lung and lymph nodes, it is more evident that EMILIN1 is distributed at the abluminal surfaces of LECs (arrows; scale bars, 45 μm). In the lymph node, EMILIN1-positive fibers connecting LECs to the surrounding ECM are evident (asterisks).</p></caption><graphic xlink:href="zmb0120875460002"></graphic></fig><fig position="float" id="f3"><label>FIG. 3.</label><caption><p>Hyperplasia and enlarged lymphatic vessels in <italic>Emilin1</italic>-deficient mice. (A and B) Immunofluorescence staining of mouse skin (A) and small intestine (B) for podoplanin (red), LYVE-1 (blue), and MMRN2 (green) revealed a higher number of enlarged lymphatic vessels in the skin (A, bottom) and in the intestines (B, bottom) of <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> mice (<italic>n</italic> = 10) than in their WT littermates (<italic>n</italic> = 10) (A and B, top). (C and D) Vessel counts per field. In a double-blind study, transversally oriented cryostat sections were observed at ×40 magnification, and the vessel density was evaluated in random fields. The number (mean ± standard error [SE]) of LYVE-1-positive vessels was significantly increased in the skin (C) (**, <italic>P</italic> < 1.5 × 10<sup>−7</sup>) and in the intestine (D) (*, <italic>P</italic> < 0.0002) of <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> mice. The numbers (mean ± SE) of MMRN2-positive blood vessels were not significantly different in the two mouse genotypes. (E) Immunofluorescence analysis of mouse skin for the proliferation marker Ki67 (green) and for podoplanin (red) showed a higher number of proliferating LECs in <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> (<italic>n</italic> = 5) than in WT (<italic>n</italic> = 5) mice. Representative images are shown above the graphs; the arrows indicate Ki67-positive LECs. The count of Ki67-positive cells per lymphatic vessel in mouse skin cryostat sections revealed a threefold-higher percentage of Ki67-positive lymphatic vessels (bottom left) and a significant increase in Ki67-positive cells per lymphatic vessel (bottom right) (mean ± SE; *, <italic>P</italic> = 0.015) in <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> mice compared to their WT littermates. Ki67 quantification analysis was performed, examining 49 WT and 55 <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> mouse lymphatic vessels. (F and G) A computer-assisted image analysis (ImageJ software) confirmed that the diameters (mean ± SE) of lymphatic vessels were significantly increased in the skin (F) (**, <italic>P</italic> < 6 × 10<sup>−6</sup>) and in the intestine (G) (*, <italic>P</italic> = 0.03) of <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> mice. E1, EMILIN1. Scale bars, 75 μm.</p></caption><graphic xlink:href="zmb0120875460003"></graphic></fig><fig position="float" id="f4"><label>FIG. 4.</label><caption><p>Hyperplasia and enlarged lymphatic vessels in lymph nodes of <italic>Emilin1</italic>-deficient mice. (A) Representative immunofluorescence images of mouse inguinal lymph node cryostat sections stained for LYVE-1 (red) and MMRN2 (green). Scale bars, 300 μm. (B) ImageJ software analysis revealed that the relative area occupied by lymphatic vessels in lymph nodes of <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> (E1−/−; <italic>n</italic> = 9) mice was significantly higher (mean ± standard error [SE]; *, <italic>P</italic> < 2 × 10<sup>−6</sup>) than in those of their WT littermates (<italic>n</italic> = 9). (C) Higher-magnification images show dilated LYVE-1-positive vessels (right). Scale bars, 75 μm. (D) The mean value ± SE of the diameters (ImageJ software analysis) of lymphatic vessels is reported. *, <italic>P</italic> < 2 × 10<sup>−7</sup>.</p></caption><graphic xlink:href="zmb0120875460004"></graphic></fig><fig position="float" id="f5"><label>FIG. 5.</label><caption><p>Abnormal lymphatic-vessel morphology in <italic>Emilin1</italic>-deficient mice. (A) Whole-mount immunofluorescence staining with LYVE-1 shows an irregular morphology of ear lymphatic vessels. The white asterisks indicate buds on lymphatic vessels. Scale bars, 300 μm. (B to D) LYVE-1 diaminobenzidine-peroxidase whole-mount staining of submucosal (B) (scale bars, 500 μm) and subserosal (C and D) (scale bars, 500 μm) lymphatic vessels. The black asterisks indicate dysmorphic structures.</p></caption><graphic xlink:href="zmb0120875460005"></graphic></fig><fig position="float" id="f6"><label>FIG. 6.</label><caption><p>Lymphangioma induction in <italic>Emilin1</italic>-deficient mice. (A) Representative images show that lymphangioma plaques were more numerous and larger in <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> mice (the arrowheads indicate the white plaques that developed on the liver and diaphragm surfaces). (B) Lymphangioma development. Class I corresponds to few and small lymphangioma plaques, class III to numerous and large plaques, and class II to an intermediate situation. (C) Lymphatic-vessel density. Lymphangioma cryostat sections were stained with LYVE-1, and in a double-blind study, lymphatic-vessel densities were evaluated as low, medium, and high. (D) Quantitative ImageJ analysis. The average fluorescence intensity confirmed that lymphatic-vessel density was significantly increased in <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> (E1−/−) and <italic>Emilin1</italic><sup><italic>+/</italic></sup><italic><sup>−</sup></italic> (E1+/−) mouse lymphangiomas compared with those of their WT littermates (*, <italic>P</italic> < 0,04; **, <italic>P</italic> < 6 × 10<sup>−5</sup>). No significant differences were observed for MMRN2-positive blood vessels. The error bars indicate standard deviations. (E) Immunofluorescence analysis of cryostat sections of mouse lymphangiomas. LYVE-1-positive lymphatic vessels (red; note that liver sinusoids are also positive) and MMRN2-positive blood vessels (green). L, liver; T, tumor. Scale bars, 75 μm. (F) Whole mounts of diaphragm plaques of WT and <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> mice stained with LYVE-1. Scale bars, 300 μm. (G) Proliferation rate. WT and <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> LECs isolated from mouse lymphangiomas (LAECs) were seeded onto glass coverslips and grown in EBM plus 2% fetal bovine serum. After 72 h, Ki67-positive nuclei per field were counted at ×60 magnification. *, <italic>P</italic> < 0.006. (H) Tube formation assay. WT and <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> LAECs were seeded onto Matrigel and allowed to form tube-like structures for 6 h. The images were acquired with a camera-equipped inverted microscope (×10 original magnification).</p></caption><graphic xlink:href="zmb0120875460006"></graphic></fig><fig position="float" id="f7"><label>FIG. 7.</label><caption><p>EMILIN1 deficiency affects LEC anchorage. Transmission electron microscopy analysis of WT (A and D) and <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> (B and E) skin lymphatic vessels. (A) WT LECs display characteristic bundles of anchoring filaments (arrows), which extend from the abluminal side of the plasma membrane into the adjoining connective tissue (inset, arrowheads). (B) <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> LECs show reduced numbers of tufts of anchoring filaments (arrow). (C) Quantitative analysis of the bundles of anchoring filaments in WT and <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> skin lymphatics (<italic>n</italic> = 10). The values express means ± standard deviations per 100 μm and show a significant reduction in the number of <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> lymphatic vessels (<italic>P</italic> < 0.005). (D) Normal lymphatic endothelium showing typical overlapping junctions (arrows) between adjacent LECs. (E) Abnormal overlapping junctions in an <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> lymphatic vessel involving several LECs (arrows); the LECs in these areas appeared thin and packed and developed adherens junctions. Scale bar, 200 nm; inset scale bar, 60 nm.</p></caption><graphic xlink:href="zmb0120875460007"></graphic></fig><fig position="float" id="f8"><label>FIG. 8.</label><caption><p>Impaired lymphatic function in <italic>Emilin1</italic>-deficient mice. (A) Evans blue dye accumulation in inguinal lymph nodes 30 min after dermal injection into the footpad; the dye is barely detectable in <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> mice (right), whereas the inguinal lymph node is easily visualized in WT mice (left). The images were acquired with a camera-equipped dissection microscope. (B) Evans blue dye contents (mean ± standard deviation [SD]) in inguinal and axillary lymph nodes expressed as percentages of the amount (ng/mg) of dye in WT lymph nodes after dermal injection into the footpad (*, <italic>P</italic> < 1.5 × 10<sup>−6</sup>; **, <italic>P</italic> < 8 × 10<sup>−7</sup>). E1−/−, <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup>. (C) Lymph leakage. Spots of Evans blue extravasation in mustard oil-treated mouse skin. (D) Quantification (mean ± SD) of Evans blue dye content in treated (*, <italic>P</italic> < 0.0085) and untreated (**, <italic>P</italic> < 6 × 10<sup>−5</sup>) skin. (E) Intravital lymphangiography. To visualize lymphatic vessels, 2 μl of 1% Evans blue dye was intradermally injected into the rims of the ears of WT (<italic>n</italic> = 5) and <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> (<italic>n</italic> = 5) mice. At 1, 3, and 5 min, the ears were photographed with a camera-equipped dissection microscope. One representative experiment is shown. The arrows indicate the major leakage areas in <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> mouse ears; the arrowheads indicate the extension of the leakage (bottom). (Right) The irregular morphology of <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> mouse lymphatic vessels is evidenced by processed images. (F) Peripheral edema. Hind limbs of WT and <italic>Emilin1</italic><sup>−</sup><sup>/</sup><sup>−</sup> mice of equal weight were compared.</p></caption><graphic xlink:href="zmb0120875460008"></graphic></fig></floats-wrap></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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