The presence of a localization signal in the 3-untranslated region of c-fos mRNA was investigated by in situ hybridization and cell fractionation techniques. Cells were transfected with chimeric gene constructs in which the ␤-globin coding region was used as a reporter and linked to either its own 3-untranslated region, the c-fos 3-untranslated region, or the c-fos 3-untranslated region containing different deletions. Replacement of the endogenous ␤-globin 3-untranslated region by that from c-fos caused a redistribution of the transcripts so that they were recovered in cytoskeletal-bound polysomes and seen localized in the perinuclear cytoplasm. Deletion of the AU-rich instability region did not affect transcript localization, but removal of a distinct 145-nucleotide region of the 3-untranslated region abolished it. The prevention of transcript translation by desferrioxamine led to a marked loss of transcript localization, independent of mRNA instability. The data show that the 3-untranslated region of c-fos mRNA, as c-myc, contains a localization signal, which targets the mRNA to the perinuclear cytoskeleton. We propose that this is important to ensure efficient nuclear import of these key regulatory proteins. mRNA localization by the fos 3-untranslated region is independent of mRNA instability, and the two are determined by different regulatory elements.

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Transposable elements with long terminal inverted repeats are rare and only one family of elements of this sort has been identified in the genome of Drosophila melanogaster. An insertion associated with the HSBS mutation of the achaete-scute complex has been reported to be a second element of this type. We have determined the complete sequence of this insertion and have shown that it is in fact two copies of a new LINE-like transposable element, that we have called BS, inserted in opposite orientation 337 bp apart. Like other elements of this type, BS has two open reading frames that appear to encode a gag-like polypeptide and a reverse transcriptase. There are few complete BS elements in the five strains of D.melanogaster that we have tested and they appear to transpose infrequently. The events that may have lead to the double BS insertion are discussed in terms of the supposed mechanism of transposition of LINE-like elements.

Body mass (BM) is a classic polygenic trait that has been extensively investigated to determine the underlying genetic architecture. Many previous studies looking at the genetic basis of variation in BM in murine animal models by quantitative trait loci (QTL) mapping have used crosses between two inbred lines. As a consequence it has not been possible to explore imprinting effects which have been shown to play an important role in the genetic basis of early growth with persistent effects throughout the growth curve. Here we use partially inbred mouse lines to identify QTL for mature BM by applying both Mendelian and Imprinting models. The analysis of an F2 population (n approximately 500) identified a number of QTL at 14, 16, and 18 weeks explaining in total 31.5%, 34.4%, and 30.5% of total phenotypic variation, respectively. On Chromosome 8 a QTL of large effect (14% of the total phenotypic variance at 14 weeks) was found to be explained by paternal imprinting. Although Chromosome 8 has not been previously associated with imprinting effects, features of candidate genes within the QTL confidence interval (CpG islands and direct clustered repeats) support the hypothesis that Insulin receptor substrate 2 may be associated with imprinting, but as yet is unidentified as being so.

Quantitative trait loci for regional adiposity in mouse lines divergently selected for food intake. Obesity. 2007;15:2994 -3004. Objective: Obesity is thought to result from an interaction between genotype and environment. Excessive adiposity is associated with a number of important comorbidities; however, the risk of obesity-related disease varies with the distribution of fat throughout the body. The aim of this study was to map quantitative trait loci (QTLs) associated with regional fat depots in mouse lines divergently selected for food intake corrected for body mass. Research Methods and Procedures: Using an F 2 intercross design (n ϭ 457), the dry mass of regional white (subcutaneous, gonadal, retroperitoneal, and mesenteric) adipose tissue (WAT) and brown adipose tissue (BAT) depots were analyzed to map QTLs. Results: The total variance explained by the mapped QTL varied between 12% and 39% for BAT and gonadal fat depots, respectively. Using the genome-wide significance threshold, nine QTLs were associated with multiple fat depots. Chromosomes 4 and 19 were associated with WAT and BAT and chromosome 9 with WAT depots. Significant sex ϫ QTL interactions were identified for gonadal fat on chromosomes 9, 16, and 19. The pattern of QTLs identified for the regional deposits showed the most similarity between retroperitoneal and gonadal fat, whereas BAT showed the least similarity to the WAT depots. Analysis of total fat mass explained in excess of 40% of total variance. Discussion: There was limited concordance between the QTLs mapped in our study and those reported previously. This is likely to reflect the unique nature of the mouse lines used. Results provide an insight into the genetic basis of regional fat distribution.