There is growing concern over confounding artifacts associated with β-cell–specific Cre-recombinase transgenic models, raising questions about their general usefulness in research. The inducible β-cell–specific transgenic (MIP-CreERT1Lphi) mouse was designed to circumvent many of these issues, and we investigated whether this tool effectively addressed concerns of ectopic expression and disruption of glucose metabolism. Recombinase activity was absent from the central nervous system using a reporter line and high-resolution microscopy. Despite increased pancreatic insulin content, MIP-CreERT mice on a chow diet exhibited normal ambient glycemia, glucose tolerance and insulin sensitivity, and appropriate insulin secretion in response to glucose in vivo and in vitro. However, MIP-CreERT mice on different genetic backgrounds were protected from high-fat/ streptozotocin (STZ)-induced hyperglycemia that was accompanied by increased insulin content and islet density. Ectopic human growth hormone (hGH) was highly expressed in MIP-CreERT islets independent of tamoxifen administration. Circulating insulin levels remained similar to wild-type controls, whereas STZ-associated increases in α-cell number and serum glucagon were significantly blunted in MIP-CreERT1Lphi mice, possibly due to paracrine effects of hGH-induced serotonin expression. These studies reveal important new insight into the strengths and limitations of the MIP-CreERT mouse line for β-cell research.

Adult social behaviour can be persistently modified by early-life social experience. In rodents, such effects are induced by tactile maternal stimulation resulting in neuroendocrine modifications of the hypothalamicpituitary -adrenal axis involved in stress responsiveness. Whether similar long-term alterations can occur in the hypothalamic -pituitary -interrenal (HPI) axis of poikilothermic vertebrates is unknown. We compared the expression of four genes of the HPI axis in adults of the cooperatively breeding cichlid Neolamprologus pulcher, which had been exposed to two early-life social treatments 1.5 years prior to brain sampling. Fish reared with parents and siblings had less brain expression of corticotropin-releasing factor and of the functional homologue of the mammalian glucocorticoid receptor (GR1) than individuals reared with same-age siblings only. Expression of the mineralocorticoid receptors (MR) did not differ between treatments, but the MR/GR1 expression ratio was markedly higher in fish reared with parents and siblings. Thus, we show here that early social experience can alter the programming of the stress axis in poikilothermic vertebrates, suggesting that this mechanism is deeply conserved within vertebrates. Moreover, we show for the first time that reprogramming of the stress axis of a vertebrate can be induced without tactile stimulation by parents.

HIV-1 infection causes depletion and/or dysfunction of distinct CD4+ T cell subsets and may affect these differently. Using the CD4C/HIV-1Nef transgenic (Tg) mice as a model, we report that HIV-1 Nef causes depletion of total CD4+ T cells, but preserves and relatively enriches CD4+ regulatory T cells (Treg). We found that Nef-mediated CD4+ Treg enrichment is the direct result of Nef expression in CD4+ T cells, occurs independently of Nef-induced lymphopenia, and most likely results from multiple mechanisms: lower apoptosis, enhanced cell division, and increased generation from precursors. Interestingly, Tg Treg relative enrichment could be reversed by enhancing Lck activity. Most importantly, we show that, in contrast to Tg helper CD4+ T cells that have lost their function, Nef-expressing CD4+ Treg retain their regulatory function in vitro and also in vivo, under some settings. In particular, we found that Treg prevent expansion of Tg B and non-Treg T cells in vivo. Our study reveals that Nef affects distinct CD4+ T cell subsets differently and uncovers the high proliferative potential of B and non-Treg T cells in this mouse model.