A novel murine gene, Sickle tail, linked to the Danforth's short tail locus, is required for normal development of the intervertebral disc

We established the mutant mouse line, B6;CB-SktGtAyu8021IMEG (SktGt), through gene-trap mutagenesis in embryonic stem cells. The novel gene identified, called Sickle tail (Skt), is composed of 19 exons and encodes a protein of 1352 amino acids. Expression of a reporter gene was detected in the notochord during embryogenesis and in the nucleus pulposus of mice. Compression of some of the nuclei pulposi in the intervertebral discs (IVDs) appeared at embryonic day (E) 17.5, resulting in a kinky-tail phenotype showing defects in the nucleus pulposus and annulus fibrosus of IVDs in SktGt/Gt mice. These phenotypes were different from those in Danforth's short tail (Sd) mice in which the nucleus pulposus was totally absent and replaced by peripheral fibers similar to those seen in the annulus fibrosus in all IVDs. The Skt gene maps to the proximal part of mouse chromosome 2, near the Sd locus. The genetic distance between them was 0.95 cM. The number of vertebrae in both [Sd +/+ SktGt] and [Sd SktGt/+ +] compound heterozygotes was less than that of Sd heterozygotes. Furthermore, the enhancer trap locus Etl4lacZ, which was previously reported to be an allele of Sd, was located in the third intron of the Skt gene.     

House mouse Mus musculus dispersal in East Eurasia inferred from 98 newly determined complete mitochondrial genome sequences

The Eurasian house mouse Mus musculus is useful for tracing prehistorical human movement related to the spread of farming. We determined whole mitochondrial DNA (mtDNA) sequences (ca. 16,000 bp) of 98 wild-derived individuals of two subspecies, M. m. musculus (MUS) and M. m. castaneus (CAS). We revealed directional dispersals reaching as far as the Japanese Archipelago from their homelands. Our phylogenetic analysis indicated that the eastward movement of MUS was characterised by five step-wise regional extension events: (1) broad spatial expansion into eastern Europe and the western part of western China, (2) dispersal to the eastern part of western China, (3) dispersal to northern China, (4) dispersal to the Korean Peninsula and (5) colonisation and expansion in the Japanese Archipelago. These events were estimated to have occurred during the last 2000–18,000 years. The dispersal of CAS was characterised by three events: initial divergences (ca. 7000–9000 years ago) of haplogroups in northernmost China and the eastern coast of India, followed by two population expansion events that likely originated from the Yangtze River basin to broad areas of South and Southeast Asia, including Sri Lanka, Bangladesh and Indonesia (ca. 4000–6000 years ago) and to Yunnan, southern China and the Japanese Archipelago (ca. 2000–3500). This study provides a solid framework for the spatiotemporal movement of the human-associated organisms in Holocene Eastern Eurasia using whole mtDNA sequences, reliable evolutionary rates and accurate branching patterns. The information obtained here contributes to the analysis of a variety of animals and plants associated with prehistoric human migration.Subject terms: Evolution, Genetic variation     

Editor's choice: Large,Male Germ Cell-Specific Hypomethylated DNA Domains With Unique Genomic and Epigenomic Features on the Mouse X Chromosome

To understand the epigenetic regulation required for germ cell-specific gene expression in the mouse, we analysed DNA methylation profiles of developing germ cells using a microarray-based assay adapted for a small number of cells. The analysis revealed differentially methylated sites between cell types tested. Here, we focused on a group of genomic sequences hypomethylated specifically in germline cells as candidate regions involved in the epigenetic regulation of germline gene expression. These hypomethylated sequences tend to be clustered, forming large (10 kb to ∼9 Mb) genomic domains, particularly on the X chromosome of male germ cells. Most of these regions, designated here as large hypomethylated domains (LoDs), correspond to segmentally duplicated regions that contain gene families showing germ cell- or testis-specific expression, including cancer testis antigen genes. We found an inverse correlation between DNA methylation level and expression of genes in these domains. Most LoDs appear to be enriched with H3 lysine 9 dimethylation, usually regarded as a repressive histone modification, although some LoD genes can be expressed in male germ cells. It thus appears that such a unique epigenomic state associated with the LoDs may constitute a basis for the specific expression of genes contained in these genomic domains.     

Molecular cloning, genetic mapping, and expression of the mouse Sf3b1 (SAP155) gene for the U2 snRNP component of spliceosome

SAP155, a subunit of the U2 snRNP, is essential for prespliceosome assembly and splicing catalysis of the major spliceosome. Moreover, the protein has been identified in the minor (U12-dependent) spliceosome. These facts strongly suggest that SAP155 is shared by two distinct complexes owing to its importance in the removal of any type of intron. Here we have isolated a cDNA encoding the 146-kDa mouse homolog, designated Sf3b1. The amino acid sequence of Sf3b1 is very highly conserved among homologs from Schizosaccharomyces pombe (52.4% identity) to human (99.6%), and the C-terminal 825 residues of these Sf3b1 homologs show even higher identities. This C-terminal region shows significant similarity to the PR65 subunit of protein phosphatase 2A, which is composed of 15 tandem repeats of a 39 amino acid sequence. Mouse genome analyses showed Sf3b1 to be a single-copy gene mapping to the central part of Chromosome (Chr) 1. Northern blot analysis and whole mount in situ hybridization revealed Sf3b1 to be ubiquitously expressed in a variety of adult tissues and mid-gestation embryos. Received: 14 June 2000 / Accepted: 19 October 2000