Genetic Disruption of Both Tryptophan Hydroxylase Genes Dramatically Reduces Serotonin and Affects Behavior in Models Sensitive to Antidepressants

The neurotransmitter serotonin (5-HT) plays an important role in both the peripheral and central nervous systems. The biosynthesis of serotonin is regulated by two rate-limiting enzymes, tryptophan hydroxylase-1 and -2 (TPH1 and TPH2). We used a gene-targeting approach to generate mice with selective and complete elimination of the two known TPH isoforms. This resulted in dramatically reduced central 5-HT levels in Tph2 knockout (TPH2KO) and Tph1/Tph2 double knockout (DKO) mice; and substantially reduced peripheral 5-HT levels in DKO, but not TPH2KO mice. Therefore, differential expression of the two isoforms of TPH was reflected in corresponding depletion of 5-HT content in the brain and periphery. Surprisingly, despite the prominent and evolutionarily ancient role that 5-HT plays in both vertebrate and invertebrate physiology, none of these mutations resulted in an overt phenotype. TPH2KO and DKO mice were viable and normal in appearance. Behavioral alterations in assays with predictive validity for antidepressants were among the very few phenotypes uncovered. These behavioral changes were subtle in the TPH2KO mice; they were enhanced in the DKO mice. Herein, we confirm findings from prior descriptions of TPH1 knockout mice and present the first reported phenotypic evaluations of Tph2 and Tph1/Tph2 knockout mice. The behavioral effects observed in the TPH2 KO and DKO mice strongly confirm the role of 5-HT and its synthetic enzymes in the etiology and treatment of affective disorders

Women in business leadership

This scholarly study is the first to compare business leadership in the Arab Gulf states in terms of the presence of female managers in various positions. It documents the status of women leaders—senior executives and managers—through a quantitative gender analysis of 2805 private and publicly listed companies in the Kingdom of Bahrain, the State of Kuwait, the Kingdom of Saudi Arabia, the Sultanate of Oman, the State of Qatar, and the United Arab Emirates. The study details the positions women hold within organizations and analyzes and compares these by country, business classification, company size, and ownership. The contribution to cross-cultural management is that these data on gender composition in the workforce highlight the low participation of women in business leadership as an issue. Furthermore, the study provides knowledge for cross-cultural managers about cultural attitudes toward women’s economic participation in this geographical area. The research offers helpful insights and important implications for government leaders in these countries as well as for educators, practitioners, and scholars who work to help prepare and advance women to leadership within this region