Bronchial smooth muscle hypoplasia in mouse embryonic lungs exposed to a laminin beta 1 chain antisense oligonucleotide

We used an antisense oligonucleotide (ODN) to inhibit laminin (Lh I) beta 1 chain synthesis in mouse embryonic lung explants and cell cultures. The OD N spanned 17 bases located 13 bases downstream the initiation codon and con tained phosphorothioate and C-5 propynyl pyrimidine modifications. Penetrat ion of the ODN into the lung explants was confirmed by fluorescein isothioc yanate (FITC) tagging. 50 mu M of antisense ODN decreased LM beta 1 chain s ynthesis by 82 +/- 6.9% with no significant changes in the synthesis of oth er LM chains. The same antisense probe but without C-5 propynyl pyrimidine modification, another 17-mer ODN complementary to the LM beta 1 initiation codon, and a 17-mer ODN complementary to the LM al initiation codon had no antisense activity. Lung explants exposed to the active LM beta 1 antisense ODN showed decreased LM-1 and collagen type IV deposition at the epithelia l-mesenchymal interface and an arrest in bronchial smooth muscle (SM) devel opment. Histological examination and cell motility assays suggested that th is arrest was due to impaired spreading and migration of SM cell precursors over the defective basement membrane (BM). Our studies indicate that beta 1-chain containing LMs play a role in bronchial myogenesis. (C) 1999 Elsevi er Science Ireland Ltd. All rights reserved.