Sexual behavior is variable between individuals, ranging from celibacy to sexual addictions. Within normal populations of individual men, ranging from young to middle aged, testosterone levels do not correlate with libido. To study the genetic mechanisms that contribute to individual differences in male sexual behavior, we used hybrid B6D2F1 male mice, which are a cross between two common inbred strains (C57BL/6J and DBA/2J). Unlike most laboratory rodent species in which male sexual behavior is highly dependent upon gonadal steroids, sexual behavior in a large proportion of these hybrid male mice after castration is independent of gonadal steroid hormones and their receptors; thus, we have the ability to discover novel genes involved in this behavior. Gene expression arrays, validation of gene candidates, and transgenic mice that overexpress one of the genes of interest were used to reveal genes involved in maintenance of male sexual behavior. Several genes related to neuroprotection and neurodegeneration were differentially expressed in the hypothalamus of males that continued to mate after castration. Male mice overexpressing the human form of one of these candidate genes, amyloid ␤ precursor protein (APP), displayed enhanced sexual behavior before castration and maintained sexual activity for a longer duration after castration compared with controls. Our results reveal a novel and unexpected relationship between APP and male sexual behavior. We speculate that declining APP during normal aging in males may contribute to the loss of sexual function.

We are investigating a nontypeable Haemophilus influenzae (NTHI) strain, R2866, isolated from a child with meningitis. R2866 is unusually resistant to killing by normal human serum. The serum 50% inhibitory concentration (IC 50 ) for this strain is 18%, approaching that of encapsulated H. influenzae. R3392 is a derivative of R2866 that was found to have increased sensitivity to human serum (IC 50 , 1.5%). Analysis of tetrameric repeat regions within lipooligosaccharide (LOS) biosynthetic genes in both strains indicated that the glycosyltransferase gene lgtC was out of frame ("off") in most colonies of R3392 but in frame with its start codon ("on") in most colonies of the parent. We sought antigenic and biochemical evidence for modification of the LOS structure. In a whole-cell enzyme-linked immunosorbent assay, strain R3392 displayed reduced binding of the Gal␣1,4Gal-specific monoclonal antibody 4C4. Mass spectrometry analysis of LOS from strain R2866 indicated that the primary oligosaccharide glycoform contained four heptose and four hexose residues, while that of R3392 contained four heptose and three hexose residues. We conclude that the R2866 lgtC gene encodes a galactosyltransferase involved in synthesis of the 4C4 epitope, as in other strains, and that expression of lgtC is associated with the high-level serum resistance that has been observed for this strain. This is the first description of the genetic basis of high-level serum resistance in NTHI, as well as the first description of LOS composition in an NTHI strain for which the complete genome sequence has been determined.The gram-negative bacterium Haemophilus influenzae is a common commensal and occasional pathogen of the upper respiratory tract. Prevalence studies have shown that H. influenzae strains isolated from the upper airway are predominately unencapsulated (nontypeable H. influenzae [NTHI]). While most disease associated with NTHI is limited to mucosal sites, a small proportion of NTHI infections are systemic. Many of these are in elderly adults, occurring as a complication of pneumonia. In the past decade, there have been several reports of NTHI strains or strains with capsules of types other than b isolated from the blood or cerebrospinal fluid (CSF) of apparently normal children who had been immunized with an H. influenzae type b (Hib) vaccine (7,8,10,38). To facilitate development of vaccines able to prevent all H. influenzae infections, an understanding of the virulence of invasive NTHI is critical.A 1996 case report was one of the first to describe NTHI meningitis in a child with normal immunological and anatomical status (36). We found that R2866, the strain isolated from this child, is nearly as resistant as a virulent type b strain, E1a, to the bactericidal effects of normal adult human serum. We demonstrated that R2866 lacks the genes for capsule synthesis and secretion. Using flow cytometry, we showed that when R2866 is incubated in 40% normal human serum, the classical pathway of complement activation is initiated normally, but t...