Targeted Deletion of all Caldesmon Splice Variants in Mice Results in Abdominal Wall Closure Defects

Ample evidence obtained in vitro indicates that the thin filament linked protein, caldesmon (CaD) is involved in regulation of smooth muscle contraction. Homozygous h-CaD deficient mice were reported to be viable and exhibit a but small slowing of relaxation (Guo et al., 2013). However, the results are confounded by upregulation of non-muscle l-CaD in smooth muscle. Thus, the in vivo function of CaD is still not clear. Here we report that deletion of all splice variants of Cald1 results in perinatal lethality whereas the life span of heterozygotes (hets) is normal. Gene targeting was achieved by deleting exons 2-13 in the murine Cald1 gene. Homologous recombination was confirmed on DNA level by Southern blots and PCR, and on protein level by Western Blotting. Homozygous offspring followed Mendelian rules at E15.5 but was abrogated at E19.5. The bodyweight of the -/- fetuses at E18.5 was reduced by ~20%. The most prominent feature of the -/- fetuses is the persistence of the physiological umbilical hernia ...