LPP (Lipoma Preferred Partner) is a zyxin-related cell adhesion protein that is involved in the regulation of cell migration. We generated mice with a targeted disruption of the Lpp gene and analysed the importance of Lpp for embryonic development and adult functions. Aberrant Mendelian inheritance in heterozygous crosses suggested partial embryonic lethality of Lpp(-/-) females. Fertility of Lpp(-/-) males was proven to be normal, however, females from Lpp(-/-) x Lpp(-/-) crosses produced a strongly reduced number of offspring, probably due to a combination of female embryonic lethality and aberrant pregnancies. Apart from these developmental and reproductive abnormalities, Lpp(-/-) mice that were born reached adulthood without displaying any additional macroscopic defects. Oil the other hand, Lpp(-/-) mouse embryonic fibroblasts exhibited reduced migration capacity, reduced viability, and reduced expression of some Lpp interaction partners. Finally, we discovered a short nuclear form of Lpp, expressed mainly in testis via an alternative promoter. (c) 2008 Elsevier Inc. All rights reserved.