Functional analysis of the cytoskeletal protein talin2 using gene disruption

Talinl is a large, ubquitously expressed cytoskeletal protein that couples integrins to the actin cytoskeleton. Analysis of genomic and EST databases shows the presence of a second Tin gene encoding a closely related protein (75% identity in human), Tln2. Disruption of both Tlnl alleles in mouse results in early embryonic lethality. Although both talinl and talin2 are very similar in sequence and most probably bind the same ligands, talin2 cannot compensate for the loss of talinl in early mouse development. To further understand the role of talin2, analysis of talin2 expression at the mRNA and protein level in mouse and human has been carried out. A genetrap cell line (BayGenomics) expressing a fusion protein talin2-p-galactosidase has been used to report on talin2 expression. This cell line was used to generate transgenic mice, which allowed the study of talin2 expression at different stages of embryonic development and in various adult mouse tissues. In order to study the role of talin2 in mammalian physiology and ontogeny, a conditional knockout approach based on a Cre-tri/ox system was used to inactivate Tln2 expression in mouse. The successful generation of a Tln2 conditional knockout mouse is reported.