New assistant professor joins NIG as of January 1, 2018.

Keita MIYOSHI: Invertebrate Genetics Laboratory, Saito Group

Mammalian Genetics Laboratory / Shiroishi Group
Genetic Informatics Laboratory / Kawamoto Group

Commonly used laboratory mouse strains have mosaic genomes, which are derived predominantly from the west European subspecies with the remaining sequences derived from the Japanese subspecies. National Institute of Genetics (NIG) has established a series of experimental mouse strains named “Mishima Battery”. It consists of ten inbred strains originated from four mouse subspecies including the Japanese subspecies, which are widely distributed in the world (Fig. 1). Most of these strains have very remote genetic status from the commonly used laboratory mouse strains such as C57BL/6J (B6), and show very unique phenotypes. Genomic polymorphisms between the laboratory strains and the Japanese subspecies-derived strains are widely used in studies of epigenetics as allele-specific markers. The mouse strains in the “Mishima Battery” are now distributed to the research community via RIKEN BioResource center and NIG, and contribute to broad range of life science. NIG has also established B6-ChrN^MSM consomic strains, in which every chromosome of B6 is substituted by corresponding chromosome of Japanese wild mouse-derived MSM/Ms strain, a member of “Mishima Battery”. Using a full panel of the consomic strains, researchers are able to identify chromosomes that control complex traits and diseases. NIG provides these consomic strains to the research community.

Our recent genome-resequencing project of “Mishima Battery” revealed over forty millions of SNPs due to large inter-subspecific genetic distance. Here, we release an upgraded version of the NIG Mouse Genome database named “NIG_MoG2” (http://molossinus.lab.nig.ac.jp/mog2/). NIG_MoG2 primarily comprises the whole genome sequence data of the “Mishima Battery” (Fig. 2), providing visualized genome polymorphism information with single-nucleotide polymorphisms and short insertions/deletions in the genomes of the “Mishima Battery”. It allows users, especially for wet-lab biologists, to intuitively recognize inter-subspecific genome divergence on the browser. NIG_MoG2 is thus a valuable navigator for exploring mouse genome polymorphisms.

This project was supported by NIG Advanced Genomics Project (Next Generation Genome-Research-Hub Project), “Genome Information Upgrading Program” of National BioResource Project (NBRP) from Japan Agency for Medical Research and Development (AMED). The project was performed as a mission of the Genetic Resource Center of NIG.

Fig. 1. Geographic distribution of mouse subspecificies, and origins of the “Mishima Battery”. Names of the strains are indicated in colored and bold prints.

Fig. 2. Top page of the NIG_MoG2 (http://molossinus.lab.nig.ac.jp/mog2).

Pressrelease(In Japanese only)

Establishment of precise neuronal connectivity in the mammalian neocortex relies on activity-dependent circuit reorganization during postnatal development; however, the nature of cortical activity during this period remains largely unknown.

Using two-photon calcium imaging of the mouse somatosensory cortex (barrel cortex) in vivo during the first postnatal week, we revealed that layer 4 (L4) cortical neurons within the same barrel fire synchronously in the absence of peripheral stimulation, creating a “patchwork” pattern of spontaneous activity corresponding to the barrel map. By generating transgenic mice expressing a genetically-coded calcium indicator GCaMP6s in thalamocortical axons, we showed that thalamocortical axons also demonstrated the spontaneous patchwork activity pattern. Patchwork activity was diminished by peripheral anesthesia but was mostly independent of self-generated whisker movements. The patchwork activity pattern largely disappeared during postnatal week 2, as even L4 neurons within the same barrel tended to fire asynchronously. This spontaneous L4 activity pattern has features suitable for circuit refinement in the neonatal barrel cortex.

This work was supported by JSPS KAKENHI grant numbers JP15K14322 and JP16H06143, the Takeda Science Foundation, and the Collaborative Research Project (2017-2923) of Brain Research Institute, Niigata University to H.M., and JSPS KAKENHI grant numbers JP16K14559, JP15H01454, and JP15H04263, and Grant-in Scientific Research on Innovation Areas “Dynamic Regulation of Brain Function by Scrap & Build System” (JP16H06459) from MEXT to T.I.

Figure: Novel type of spontaneous activity found in the mouse somatosensory cortex layer 4 in neonates.

(a) Five rows (A-E) of whiskers on the snout.

(b) In the barrel cortex layer 4 (L4), barrels are arranged in a one-to-one correspondence with whiskers on the snout and process tactile information derived from individual whiskers. Each barrel contains hundreds of neurons processing sensory information from the corresponding whisker. For example, the C1 barrel (arrow) processes information from the C1 whisker (arrow in (a)). Barrels are labeled with a red fluorescent protein.

(c)　Higher magnification image of the white square region in (b).

(d) Activity pattern of barrel cortex layer 4 at postnatal day 5, which looks like a “patchwork”. Each color represents a different activity event.