Development and function of T cells in mice with a disrupted CD2 gene.

CD2 is a T cell surface glycoprotein that mediates cellular adhesion and can participate in signal transduction. It is expressed early in thymocyte ontogeny and consequently has been proposed to participate in T cell development. To study the in vivo function of CD2, the murine gene was inactivated using the technique of homologous recombination in embryonic stem cells. Homozygous mutant mice are healthy and have an apparently normal complement of lymphocytes. They mount effective immune responses similar to those of wild type controls. In particular, the generation and function of cytotoxic T cells was found to be normal as was the production of antibodies following immunization. Selection of thymocytes expressing either MHC class I- or class II-restricted transgenic T cell receptors was also grossly normal in the absence of CD2. Thus, CD2 may be dispensable for the development and function of T cells. Within the context of other targetted mutations, these mice should be useful in defining the precise roles of various cell surface molecules involved in T cell responses.     

Adult onset lung disease following transient disruption of fetal stretch-induced differentiation

One of the mechanisms by which adult disease can arise from a fetal origin is by in utero disruption of organogenesis. These studies were designed to examine respiratory function changes in aging rats following transient disruption of lung growth at 16 days gestation. Fetuses were treated in utero with a replication deficient adenovirus containing the cystic fibrosis conductance transmembrane regulator (CFTR) gene fragment cloned in the anti-sense direction. The in utero-treated rats demonstrated abnormal lung function beginning as early as 30 days of age and the pathology progressed as the animals aged. The pulmonary function abnormalities included decreased static compliance as well as increased conducting airway resistance, tissue damping, and elastance. Pressure volume (PV) curves demonstrated a slower early rise to volume and air trapping at end-expiration. The alterations of pulmonary function correlated with lung structural changes determined by morphometric analysis. These studies demonstrate how transient disruption of lung organogensis by single gene interference can result in progressive change in lung function and structure. They illustrate how an adult onset disease can arise from subtle changes in gene expression during fetal development.     

Central place foraging in Rattus norvegicus

Rats could accumulate food pellets by responding on one lever, and then gain access to them by responding on a second lever N times (experiment 1), by ceasing to respond on the first lever for D seconds (experiment 2), or by making a single, vigorous response of force W on the second lever (experiment 3). The design may be viewed as an analogue of central place foraging. As N (distance), D (time), or W (effort) increased, load (the average number of pellets accumulated before they were eaten) also increased. It appeared that delay mediated the effect of the other independent variables. A simple model of central place foraging was shown to accommodate the data.