Purification and physical properties of the male and female double sex proteins of Drosophila.

The double sex gene (dsx) encodes two proteins, DSX(M) and DSX(F), that regulate sex-specific transcription in Drosophila. These proteins bind target sites in DNA from which the male-specific DSX(M) represses and the female-specific DSX(F) activates transcription of yolk protein (Yp) genes. We investigated the physical properties of these DSX proteins, which are identical in their amino-terminal 397 residues but are entirely different in their carboxyl-terminal sequences (DSX(F), 30 amino acids; DSX(M), 152 amino acids). DSX(M) and DSX(F) were overexpressed in cultured insect cells and purified to near homogeneity. Gel filtration chromatography and glycerol gradient sedimentation showed that at low concentrations both proteins are dimers of highly asymmetrical shape. The axial ratios are approximately 18:1 (DSX(M), 860 X 48 angstroms; DSX(F), 735 X 43 angstroms). At higher concentrations, the proteins form tetramers. Through use of a novel, double crosslinking assay (protein-DNA plus protein-protein), we demonstrated that a DNA regulatory site binds to both monomers of the DSX dimer and to only two monomers of the tetramer. Furthermore, binding another DNA molecule to what we presume is the second and identical site in the tetramer dramatically shifts the equilibrium from tetramers to dimers. These oligomerization and DNA binding properties are indistinguishable between the male and female proteins.

Mutant oocytic low density lipoprotein receptor gene family member causes atherosclerosis and female sterility.

The so-called very low density lipoprotein receptors (VLDLRs) are related to the LDLR gene family. So far, naturally occurring mutations have only been described for the prototype LDLR; in humans, they cause familial hypercholesterolemia. Here we describe a naturally occurring mutation in a VLDLR that causes a dramatic abnormal phenotype. Hens of the mutant restricted-ovulator chicken strain carry a single mutation, lack functional oocyte receptors, are sterile, and display severe hyperlipidemia with associated premature atherosclerosis. The mutation converts a cysteine residue into a serine, resulting in an unpaired cysteine and greatly reduced expression of the mutant avian VLDLR on the oocyte surface. Extraoocytic cells in the mutant produce higher than normal amounts of a differentially spliced form of the receptor that is characteristic for somatic cells but absent from germ cells.

Modulation of pair bonding in female prairie voles (Microtus ochrogaster) by corticosterone.

Glucocorticoid levels in animals may respond to and influence the development of social attachments. This hypothesis was tested in prairie voles (Microtus ochrogaster), monogamous rodents that form long-term heterosexual pair bonds. In socially naive female prairie voles, cohabitation with an unfamiliar male resulted in a dramatic decline in serum corticosterone levels. When corticosterone levels were reduced via adrenalectomy, females developed partner preferences after 1 h of cohabitation, while sham-operated and untreated females required 3 h or more of nonsexual cohabitation to establish a partner preference. In adrenalectomized and intact females, exogenous injections of corticosterone, given prior to social exposure, prevented the development of preferences for the cohabitating male. Although corticosterone inhibited the development of partner preferences, it did not interfere with the expression of previously established social preferences. These results suggest that social stimuli can modulate adrenal activity and that adrenal activity, in turn, is capable of influencing the formation of adult social preferences in female prairie voles. The involvement of the adrenal axis in the formation of partner preferences and the subsequent development of pair bonds provides a mechanism through which environmental and social factors may influence social organization in this species.