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Compound Genetic Ablation of Nidogen 1 and 2 Causes Basement Membrane Defects and Perinatal Lethality in Mice

Bernhard L. Bader ,^1,, Neil Smyth,^2,, Sabine Nedbal,¹ Nicolai Miosge,³ Anke Baranowsky,⁴ Sharada Mokkapati,⁴ Monzur Murshed,⁵ and Roswitha Nischt^4*

Department of Molecular Biology, Max Planck Institute for Biochemistry, D-82152 Martinsried, Germany,¹ Institute for Biochemistry II and Center of Molecular Medicine, University of Cologne, D-50924 Cologne, Germany,² Department of Histology, University of Göttingen, D-37075 Göttingen, Germany,³ Department of Dermatology, University of Cologne, D-50924 Cologne, Germany,⁴ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030⁵

Received 21 December 2004/ Returned for modification 24 February 2005/ Accepted 4 May 2005

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.

B.L.B. and N.S. contributed equally to this work.

Present address: Department of Nutritional Medicine, Technical University Munich, D-85350 Freising, Germany.

Present address: School of Biological Sciences, University of Southampton, Southampton, United Kingdom.

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