Heritable variation in locomotion,reward sensitivity and impulsive behaviors in a genetically diverse inbred mouse panel

Drugs of abuse, including alcohol and stimulants like cocaine, produce effects that are subject to individual variability, and genetic variation accounts for at least a portion of those differences. Notably, research in both animal models and human subjects point toward reward sensitivity and impulsivity as being trait characteristics that predict relatively greater positive subjective responses to stimulant drugs. Here we describe use of the eight collaborative cross (CC) founder strains and 38 (reversal learning) or 10 (all other tests) CC strains to examine the heritability of reward sensitivity and impulsivity traits, as well as genetic correlations between these measures and existing addiction-related phenotypes. Strains were all tested for activity in an open field and reward sensitivity (intake of chocolate BOOST®). Mice were then divided into two counterbalanced groups and underwent reversal learning (impulsive action and waiting impulsivity) or delay discounting (impulsive choice). CC and founder mice show significant heritability for impulsive action, impulsive choice, waiting impulsivity, locomotor activity, and reward sensitivity, with each impulsive phenotype determined to be non-correlating, independent traits. This research was conducted within the broader, inter-laboratory effort of the Center for Systems Neurogenetics of Addiction (CSNA) to characterize CC and DO mice for multiple, cocaine abuse related traits. These data will facilitate the discovery of genetic correlations between predictive traits, which will then guide discovery of genes and genetic variants that contribute to addictive behaviors.     

Excision of mutagenic replication-blocking lesions suppresses cancer but promotes cytotoxicity and lethality in nitrosamine-exposed mice

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Cytomegalovirus Infection in Children Undergoing Open-Heart Surgery

A group of 124 children undergoing open-heart surgery was followed prospectively in order to estimate the risk of cytomegalovirus (CMV) infection due to transfused blood.     

Characterization of radiolabeled components of human sperm surface and seminal plasma

Externally oriented components on the human sperm cell surface and components in human seminal plasma were labeled by enzymatic iodination with lactoperoxidase and [¹²⁵I] NaI. SDS-7.5% PAGE of labeled sperm surface resolved one minor and four major components with approximate molecular weights of 92, 72, 46, 30, and 20K daltons, respectively. SDS-7.5% PAGE of labeled seminal plasma resolved five components with approximate molecular weights of 74, 51, 43, 28, and 20K daltons. Three of the five moieties seen on the sperm surface and in seminal plasma were similar in molecular weight. This suggested that these surface components were adsorbed from seminal secretions. Because the iodination procedure used labels both proteins and lipids, labeled sperm surface and labeled seminal plasma were subjected to isopycnic density gradient centrifugation to identify the chemical composition of the radioiodinated components. With human sperm surface, two areas of radioactivity were resolved in CsCl gradients, one corresponding to protein and the other to lipid. With human seminal plasma, only one area of radioactivity, corresponding to protein, was identified. Electrophoretic analysis of each peak of radioactivity obtained from the gradients demonstrated that all of the sperm surface and four of five seminal plasma components were in the protein fractions. All three of the seminal plasma components which correspond to sperm surface components were recovered in the protein fraction. This observation supports our hypothesis that some of the proteins labeled on the human sperm cell surface are adsorbed from seminal secretions.     

Genetic and Physical Mapping of the Dreher Locus on Mouse Chromosome 1

Mutations in the mouse dreher (dr) gene cause skeletal defects, hyperactivity, abnormal gait, deafness, white belly spotting, and hypoplasia of Müllerian duct derivatives. To map dr to high resolution, we utilized two crosses. Initially, we analyzed an intersubspecific intercross to construct a detailed genetic map of simple sequence length polymorphism markers within a 6.3-cM region surrounding the dr locus. Subsequently, we analyzed a second intersubspecific intercross segregating for the dr(6J) allele, which positioned dr within a 0.13-cM region between Rxrg and D1Mit370. A physical contig of BAC clones spanning the dr critical region was constructed, and eight potential dr candidate genes were excluded by genetic or physical mapping. Together these results lay the foundation for positional cloning of the dr gene.