Chromosome substitution strains (CSSs) have been proposed as a simple and powerful way to identify quantitative trait loci (QTLs) affecting developmental, physiological, and behavioral processes. Here, we report the construction of a complete CSS panel for a vertebrate species. The CSS panel consists of 22 mouse strains, each of which carries a single chromosome substituted from a donor strain (A/J) onto a common host background (C57BL/6J). A survey of 53 traits revealed evidence for 150 QTLs affecting serum levels of sterols and amino acids, diet-induced obesity, and anxiety. These results demonstrate that CSSs greatly facilitate the detection and identification of genes that control the wide diversity of naturally occurring phenotypic variation in the A/J and C57BL/6J inbred strains.

Summary Cre-loxP technology enables specific examination of the function and development of individual nuclei in the complex brain network. However, for most brain regions, the utilization of this technique has been hindered by the lack of mouse lines with Cre expression restricted to these regions. Here, we identified brain expressions of three transgenic Cre lines previously thought to be pancreas-specific. Cre expression driven by the rat-insulin promoter (Rip-Cre) was found mainly in the arcuate nucleus, and to a lesser degree in other hypothalamic regions. Cre expression driven by the neurogenin 3 promoter (Ngn3-Cre mice) was found in the ventromedial hypothalamus. Cre expression driven by the pancreas-duodenum homeobox 1 promoter (Pdx1-Cre) was found in several hypothalamic nuclei, the dorsal raphe and inferior olivary nuclei. Interestingly, Pdx1-Cre mediated deletion of vesicular GABA transporter led to postnatal growth retardation while Ngn3-Cre mediated deletion had no effects, suggesting a role for Pdx1-Cre neurons, but not pancreas, in the regulation of postnatal growth. These results demonstrate the potential for these Cre lines to study the function and development of brain neurons.