Targeted deletion of Actb demonstrates that the β-actin gene, in contrast to the γ-actin gene, is an essential gene uniquely required for cell growth and migration. Cell motility and growth defects in β-actin–knockout primary cells are due to a specific role for β-actin in regulating gene expression through control of the cellular G-actin pool.

Actins are among the most highly expressed proteins in eukaryotes and play a central role in nearly all aspects of cell biology. While the intricate process of development undoubtedly requires a properly regulated actin cytoskeleton, little is known about the contributions of different actin isoforms during embryogenesis. Of the six actin isoforms, only the two cytoplasmic actins, β cytoand γ cyto -actin, are ubiquitously expressed. We found that γ cyto -actin null (Actg1 −/− ) mice were fully viable during embryonic development, but most died within 48 hours of birth due to respiratory failure and cannibalization by the parents. While no morphogenetic defects were identified, Actg1 −/− mice exhibited stunted growth during embryonic and postnatal development as well as delayed cardiac outflow tract formation that resolved by birth. Using primary mouse embryonic fibroblasts, we confirm that γ cyto -actin is not required for cell migration. The Actg1 −/− cells, however, exhibited growth impairment and reduced cell viability, defects which perhaps contribute to the stunted growth and developmental delays observed in Actg1 −/− embryos. Since the total amount of actin protein was maintained in Actg1 −/− cells, our data suggests a distinct requirement for γ cyto -actin in cell growth and survival.

GnRH II (pGlu-His-Trp-Ser-Try-Gly-Leu-Arg-Pro-GlyNH2), an evolutionarily conserved member of the GnRH family, stimulates reproductive behavior in a number of vertebrates. To explore a role for GnRH II in regulating primate sexual behavior, eight adult female common marmosets, each fitted with an indwelling intracerebroventricular (icv) cannula, were ovariectomized, implanted subcutaneously with empty (n = 4) or estradiol-filled (n = 4) SILASTIC brand capsules, and pair housed with an adult male mate. After icv infusion of vehicle or peptides, females were placed in an observation cage for 90 min, out of visual contact with other marmosets, before the 30-min behavioral test with their male partner. Compared with vehicle, GnRH II (1 and 10 microg) increased the total number of proceptive (sexual solicitation) behaviors (tongue flicking, proceptive stares, and frozen postures) exhibited by females toward their pair mates and specifically increased the frequency of freeze postures. Effects were maximal at 1 microg and not dependent upon estradiol supplementation. GnRH II agonists/GnRH I antagonists 135-18 (1 microg) and 132-25 (1 microg), which stimulate inositol phosphate production via the marmoset type II receptor, increased the frequency of total proceptive behavior but did not specifically stimulate freeze-posture behavior. In contrast, GnRH I, at 1 mug, did not alter the frequency of proceptive behaviors. Female receptivity (female compliance with male sexual behavior) was not altered by any of the peptides tested. These findings implicate a role for GnRH II and the cognate GnRH type II receptor in stimulating female marmoset sexual behavior.

α-Dystrobrevin is a component of the dystrophin-glycoprotein complex (DGC) and is thought to have both structural and signaling roles in skeletal muscle. Mice deficient for α-dystrobrevin (adbn−/−) exhibit extensive myofiber degeneration and neuromuscular junction abnormalities. However, the biochemical stability of the DGC and the functional performance of adbn−/− muscle have not been characterized. Here we show that the biochemical association between dystrophin and β-dystroglycan is compromised in adbn−/− skeletal muscle, suggesting that α-dystrobrevin plays a structural role in stabilizing the DGC. However, despite muscle cell death and DGC destabilization, costamere organization and physiological performance is normal in adbn−/− skeletal muscle. Our results demonstrate that myofiber degeneration alone does not cause functional deficits and suggests that more complex pathological factors contribute to the development of muscle weakness in muscular dystrophy.

The actin gene family is highly conserved across eukaryotic species, and its family members share a high degree of protein sequence homology. Despite a wealth of knowledge on the structural and functional properties of actin in general, the distinct characteristics of the individual actin isoforms are only beginning to be understood. Recent animal models have provided considerable insight into the unique functions of the different actin isoforms. Additionally, evidence is emerging that the different isoforms have distinct structural and biochemical properties that likely relate to their unique functions. Furthermore, specific regulatory elements and nucleotide coding sequence differences are thought to confer functional specificity to the actin isoforms. Continued elucidation of the functional distinctions between actin isoforms will further our knowledge of the pathophysiology underlying actin-related diseases.