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Compound genetic ablation of nidogen 1 and 2 causes basement membrane defects and perinatal lethality in mice

Compound genetic ablation of nidogen 1 and 2 causes basement membrane defects and perinatal lethality in mice
Compound genetic ablation of nidogen 1 and 2 causes basement membrane defects and perinatal lethality in mice
Nidogen 1 and 2 are basement membrane glycoproteins, and previous biochemical and functional studies indicate that they may play a crucial role in basement membrane assembly. While they show a divergent expression pattern in certain adult tissues, both have a similar distribution during development. Gene knockout studies in mice demonstrated that the loss of either isoform has no effect on basement membrane formation and organ development, suggesting complementary functions. Here, we show that this is indeed the case. Deficiency of both nidogens in mice resulted in perinatal lethality. Nidogen 1 and 2 do not appear to be crucial in establishing tissue architecture during organ development; instead, they are essential for late stages of lung development and for maintenance and/or integrity of cardiac tissue. These organ defects are not compatible with postnatal survival. Ultrastructural analysis suggests that the phenotypes directly result from basement membrane changes. However, despite the ubiquitous presence of nidogens in basement membranes, defects do not occur in all tissues or in all basement membranes, suggesting a varying spectrum of roles for nidogens in the basement membrane.
0270-7306
6846-6856
Bader, Bernhard L.
f020d1af-7435-44cd-9be6-4ec39aaadfe7
Smyth, Neil
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Nedbal, Sabine
1935692f-5583-40fa-80d5-a30fd31e8a9e
Miosge, Nicolai
42183824-e9e3-49b8-a191-3f07af6ca70d
Baranowsky, Anke
0f3869ce-94e3-4f5e-b1c6-b6069b77a200
Mokkapati, Sharada
2450f3e7-fbb4-4ec3-a856-b74035a2370a
Murshed, Mokkapati
81f0f2c5-bdd1-45f8-9518-9f2a96102291
Nischt, Roswitha
a21a90aa-1297-42f1-acff-25b2fdb890e5
Bader, Bernhard L.
f020d1af-7435-44cd-9be6-4ec39aaadfe7
Smyth, Neil
0eba2a40-3b43-4d40-bb64-621bd7e9d505
Nedbal, Sabine
1935692f-5583-40fa-80d5-a30fd31e8a9e
Miosge, Nicolai
42183824-e9e3-49b8-a191-3f07af6ca70d
Baranowsky, Anke
0f3869ce-94e3-4f5e-b1c6-b6069b77a200
Mokkapati, Sharada
2450f3e7-fbb4-4ec3-a856-b74035a2370a
Murshed, Mokkapati
81f0f2c5-bdd1-45f8-9518-9f2a96102291
Nischt, Roswitha
a21a90aa-1297-42f1-acff-25b2fdb890e5

Bader, Bernhard L., Smyth, Neil, Nedbal, Sabine, Miosge, Nicolai, Baranowsky, Anke, Mokkapati, Sharada, Murshed, Mokkapati and Nischt, Roswitha (2005) Compound genetic ablation of nidogen 1 and 2 causes basement membrane defects and perinatal lethality in mice. Molecular and Cellular Biology, 25 (15), 6846-6856. (doi:10.1128/MCB.25.15.6846-6856.2005).

Record type: Article

Abstract

Nidogen 1 and 2 are basement membrane glycoproteins, and previous biochemical and functional studies indicate that they may play a crucial role in basement membrane assembly. While they show a divergent expression pattern in certain adult tissues, both have a similar distribution during development. Gene knockout studies in mice demonstrated that the loss of either isoform has no effect on basement membrane formation and organ development, suggesting complementary functions. Here, we show that this is indeed the case. Deficiency of both nidogens in mice resulted in perinatal lethality. Nidogen 1 and 2 do not appear to be crucial in establishing tissue architecture during organ development; instead, they are essential for late stages of lung development and for maintenance and/or integrity of cardiac tissue. These organ defects are not compatible with postnatal survival. Ultrastructural analysis suggests that the phenotypes directly result from basement membrane changes. However, despite the ubiquitous presence of nidogens in basement membranes, defects do not occur in all tissues or in all basement membranes, suggesting a varying spectrum of roles for nidogens in the basement membrane.

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Published date: August 2005

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Local EPrints ID: 38024
URI: https://eprints.soton.ac.uk/id/eprint/38024
ISSN: 0270-7306
PURE UUID: 4594e6e6-e330-4a66-88f4-1bb19e64b7f7

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Date deposited: 30 May 2006
Last modified: 17 Jul 2017 15:40

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Contributors

Author: Bernhard L. Bader
Author: Neil Smyth
Author: Sabine Nedbal
Author: Nicolai Miosge
Author: Anke Baranowsky
Author: Sharada Mokkapati
Author: Mokkapati Murshed
Author: Roswitha Nischt

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