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Essential role for complex N-glycans in forming an organized layer of bronchial epithelium.
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| Zeitschriftentitel: | Proceedings of the National Academy of Sciences |
|---|---|
| Personen und Körperschaften: | , , |
| In: | Proceedings of the National Academy of Sciences, 93, 1996, 20, S. 11041-11046 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Proceedings of the National Academy of Sciences
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| Schlagwörter: |
| author_facet |
Ioffe, E Liu, Y Stanley, P Ioffe, E Liu, Y Stanley, P |
|---|---|
| author |
Ioffe, E Liu, Y Stanley, P |
| spellingShingle |
Ioffe, E Liu, Y Stanley, P Proceedings of the National Academy of Sciences Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. Multidisciplinary |
| author_sort |
ioffe, e |
| spelling |
Ioffe, E Liu, Y Stanley, P 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.93.20.11041 <jats:p>Mice lacking the complex subset of N-glycans due to inactivation of the Mgat1 gene die at mid-gestation, making it difficult to identify specific biological functions for this class of cell surface carbohydrates. To circumvent this embryonic lethality and to uncover tissue-specific functions for complex N-glycans, WW6 embryonic stem cells with inactivated Mgat1 alleles were tracked in chimeric embryos. The Mgat1 gene encodes N-acetylglucosaminyltransferase I (Glc-NAc-TI; EC 2.4.1.101), the transferase that initiates the synthesis of complex N-glycans. WW6 cells carry an inert beta-globin transgene that allows their identification in chimeras by DNA-DNA in situ hybridization. Independent Mgat1-/- and Mgat1+/- mutant WW6 isolates contributed like parent WW6 cells to the tissues of embryonic day (E) 10.5 to E16.5 chimeras. However, a cell type-specific difference was observed in lung. Homozygous null Mgat1-/- WW6 cells did not contribute to the epithelial layer in more than 99% bronchi. This deficiency was corrected by transfection of a Mgat1 transgene. Interestingly, heterozygous Mgat1+/- WW6 cells were also deficient in populating the layer of bronchial epithelium. Furthermore, examination of lung bud in E9.5 Mgat1-/- mutant embryos showed complete absence of an organized epithelial cell layer in the bronchus. Thus, complex N-glycans are required to form a morphologically recognizable bronchial epithelium, revealing an in vivo, cell type-specific function for this class of N-glycans.</jats:p> Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. Proceedings of the National Academy of Sciences |
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Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. |
| title_unstemmed |
Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. |
| title_full |
Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. |
| title_fullStr |
Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. |
| title_full_unstemmed |
Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. |
| title_short |
Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. |
| title_sort |
essential role for complex n-glycans in forming an organized layer of bronchial epithelium. |
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Multidisciplinary |
| url |
http://dx.doi.org/10.1073/pnas.93.20.11041 |
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1996 |
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11041-11046 |
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<jats:p>Mice lacking the complex subset of N-glycans due to inactivation of the Mgat1 gene die at mid-gestation, making it difficult to identify specific biological functions for this class of cell surface carbohydrates. To circumvent this embryonic lethality and to uncover tissue-specific functions for complex N-glycans, WW6 embryonic stem cells with inactivated Mgat1 alleles were tracked in chimeric embryos. The Mgat1 gene encodes N-acetylglucosaminyltransferase I (Glc-NAc-TI; EC 2.4.1.101), the transferase that initiates the synthesis of complex N-glycans. WW6 cells carry an inert beta-globin transgene that allows their identification in chimeras by DNA-DNA in situ hybridization. Independent Mgat1-/- and Mgat1+/- mutant WW6 isolates contributed like parent WW6 cells to the tissues of embryonic day (E) 10.5 to E16.5 chimeras. However, a cell type-specific difference was observed in lung. Homozygous null Mgat1-/- WW6 cells did not contribute to the epithelial layer in more than 99% bronchi. This deficiency was corrected by transfection of a Mgat1 transgene. Interestingly, heterozygous Mgat1+/- WW6 cells were also deficient in populating the layer of bronchial epithelium. Furthermore, examination of lung bud in E9.5 Mgat1-/- mutant embryos showed complete absence of an organized epithelial cell layer in the bronchus. Thus, complex N-glycans are required to form a morphologically recognizable bronchial epithelium, revealing an in vivo, cell type-specific function for this class of N-glycans.</jats:p> |
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| description | <jats:p>Mice lacking the complex subset of N-glycans due to inactivation of the Mgat1 gene die at mid-gestation, making it difficult to identify specific biological functions for this class of cell surface carbohydrates. To circumvent this embryonic lethality and to uncover tissue-specific functions for complex N-glycans, WW6 embryonic stem cells with inactivated Mgat1 alleles were tracked in chimeric embryos. The Mgat1 gene encodes N-acetylglucosaminyltransferase I (Glc-NAc-TI; EC 2.4.1.101), the transferase that initiates the synthesis of complex N-glycans. WW6 cells carry an inert beta-globin transgene that allows their identification in chimeras by DNA-DNA in situ hybridization. Independent Mgat1-/- and Mgat1+/- mutant WW6 isolates contributed like parent WW6 cells to the tissues of embryonic day (E) 10.5 to E16.5 chimeras. However, a cell type-specific difference was observed in lung. Homozygous null Mgat1-/- WW6 cells did not contribute to the epithelial layer in more than 99% bronchi. This deficiency was corrected by transfection of a Mgat1 transgene. Interestingly, heterozygous Mgat1+/- WW6 cells were also deficient in populating the layer of bronchial epithelium. Furthermore, examination of lung bud in E9.5 Mgat1-/- mutant embryos showed complete absence of an organized epithelial cell layer in the bronchus. Thus, complex N-glycans are required to form a morphologically recognizable bronchial epithelium, revealing an in vivo, cell type-specific function for this class of N-glycans.</jats:p> |
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| spelling | Ioffe, E Liu, Y Stanley, P 0027-8424 1091-6490 Proceedings of the National Academy of Sciences Multidisciplinary http://dx.doi.org/10.1073/pnas.93.20.11041 <jats:p>Mice lacking the complex subset of N-glycans due to inactivation of the Mgat1 gene die at mid-gestation, making it difficult to identify specific biological functions for this class of cell surface carbohydrates. To circumvent this embryonic lethality and to uncover tissue-specific functions for complex N-glycans, WW6 embryonic stem cells with inactivated Mgat1 alleles were tracked in chimeric embryos. The Mgat1 gene encodes N-acetylglucosaminyltransferase I (Glc-NAc-TI; EC 2.4.1.101), the transferase that initiates the synthesis of complex N-glycans. WW6 cells carry an inert beta-globin transgene that allows their identification in chimeras by DNA-DNA in situ hybridization. Independent Mgat1-/- and Mgat1+/- mutant WW6 isolates contributed like parent WW6 cells to the tissues of embryonic day (E) 10.5 to E16.5 chimeras. However, a cell type-specific difference was observed in lung. Homozygous null Mgat1-/- WW6 cells did not contribute to the epithelial layer in more than 99% bronchi. This deficiency was corrected by transfection of a Mgat1 transgene. Interestingly, heterozygous Mgat1+/- WW6 cells were also deficient in populating the layer of bronchial epithelium. Furthermore, examination of lung bud in E9.5 Mgat1-/- mutant embryos showed complete absence of an organized epithelial cell layer in the bronchus. Thus, complex N-glycans are required to form a morphologically recognizable bronchial epithelium, revealing an in vivo, cell type-specific function for this class of N-glycans.</jats:p> Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. Proceedings of the National Academy of Sciences |
| spellingShingle | Ioffe, E, Liu, Y, Stanley, P, Proceedings of the National Academy of Sciences, Essential role for complex N-glycans in forming an organized layer of bronchial epithelium., Multidisciplinary |
| title | Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. |
| title_full | Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. |
| title_fullStr | Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. |
| title_full_unstemmed | Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. |
| title_short | Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. |
| title_sort | essential role for complex n-glycans in forming an organized layer of bronchial epithelium. |
| title_unstemmed | Essential role for complex N-glycans in forming an organized layer of bronchial epithelium. |
| topic | Multidisciplinary |
| url | http://dx.doi.org/10.1073/pnas.93.20.11041 |