Mice carrying a complete deletion of the talin2 coding sequence are viable and fertile.

Mice homozygous for several Tln2 gene targeted alleles are viable and fertile. Here we show that although the expression of talin2 protein is drastically reduced in muscle from these mice, other tissues continue to express talin2 albeit at reduced levels. We therefore generated a Tln2 allele lacking the entire coding sequence (Tln2(cd)). Tln2(cd/cd) mice were viable and fertile, and the genotypes of Tln2(cd/+) intercrosses were at the expected Mendelian ratio. Tln2(cd/cd) mice showed no major difference in body mass or the weight of the major organs compared to wild-type, although they displayed a mildly dystrophic phenotype. Moreover, Tln2(cd/cd) mouse embryo fibroblasts showed no obvious defects in cell adhesion, migration or proliferation. However, the number of Tln2(cd/cd) pups surviving to adulthood was variable suggesting that such mice have an underlying defect.

Endothelial cell talin1 is essential for embryonic angiogenesis.

Using Tln1(fl/fl);CreER mice, we show that tamoxifen-induced inactivation of the talin1 gene throughout the embryo produces an angiogenesis phenotype that is restricted to newly forming blood vessels. The phenotype has a rapid onset in early embryos, resulting in vessel defects by 48 h and death of the embryo within 72 h. Very similar vascular defects were obtained using a Tie2-Cre endothelial cell-specific Tln1 knockout, a phenotype that was rescued by expression of a Tln1 mini-gene in endothelial cells. We show that endothelial cells, unlike most other cell types, do not express talin2, which can compensate for loss of talin1, and demonstrate for the first time that endothelial cells in vivo lacking talin1 are unable to undergo the cell spreading and flattening required to form vessels.

Talin 2 is a large and complex gene encoding multiple transcripts and protein isoforms.

Talins are large adaptor proteins that link the integrin family of adhesion molecules to F-actin. In vertebrates, there are two talin genes. Talin 1 is essential for integrin-mediated cell adhesion; the role of talin 2 is unclear. Here we report a detailed analysis of mammalian talin 2. This reveals the existence of a previously unrecognized promoter associated with a CpG island, and separated from the first coding exon by numerous alternatively spliced noncoding exons spanning > 200 kb. Analysis of a mouse gene trap line shows that this promoter accounts for most of the talin 2 expression in adult tissues. We also demonstrate that testis and kidney express truncated talin 2 isoforms that lack the N-terminal half of the protein, and provide evidence for the developmentally regulated expression of the short testis-specific talin 2 isoform in elongating spermatids. Finally, we identify four tissue-specific alternative splicing events within the coding region of talin 2.