Provided herein are genetic constructs comprising genetic perturbation cassettes and methods of using such to assess the timing and order of gene expression.

A transgenic insect includes a genome which has at least one first exogenic DNA sequence, which is coded for a human membrane transporter protein. The expression of the first exogenic DNA sequence leads to a functional human membrane transporter protein in the transgenic insect.

The present invention relates to the method and use of reef coral fluorescent proteins in making transgenic red, green and yellow fluorescent zebrafish. Preferably, such fluorescent zebrafish are fertile and used to establish a population of transgenic zebrafish and to provide to the ornamental fish industry for the purpose of marketing. Thus, new varieties of ornamental fish of different fluorescence colors from a novel source are developed.

This application relates to therapeutic siRNA agents and methods of making and using the agents.

Provided are a method for producing a spermatogenic stem cell-like cell from a primordial germ cell-like cell derived from an isolated pluripotent stem cell in vitro, the method including (1) a step of coculturing a primordial germ cell-like cell with a gonad somatic cell in suspension to give reconstituted testis, and (2) a step of culturing the obtained reconstituted testis at gas/liquid interface to induce a DDX4-positive and PLZF-positive cell in the reconstituted testis; and
a method for producing a GSC-like cell, including dissociating a spermatogenic stem cell-like cell obtained by the method from the reconstituted testis, and culturing the cell under conditions that can induce a germline stem cell from the spermatogenic stem cell.

A transgenic non-human animal is provided. In certain embodiments, the animal comprises a genome comprising an immunoglobulin heavy chain locus comprising: a) a transcribed gene encoding a fusion protein comprising, from N-terminus to C-terminus: i. a scaffold comprising a first binding domain; and ii. a heavy chain constant region operably linked to the scaffold; wherein the scaffold is capable of specifically binding to a target in the absence of additional polypeptides; and b) a plurality of pseudogenes that are operably linked to the transcribed gene and that donate, by gene conversion, nucleotide sequence to the part of the transcribed gene that encodes the binding domain.

The invention provides engineered RNA precursors that when expressed in a cell are processed by the cell to produce targeted small interfering RNAs (siRNAs) that selectively silence targeted genes (by cleaving specific mRNAs) using the cell's own RNA interference (RNAi) pathway. By introducing nucleic acid molecules that encode these engineered RNA precursors into cells in vivo with appropriate regulatory sequences, expression of the engineered RNA precursors can be selectively controlled both temporally and spatially, i.e., at particular times and/or in particular tissues, organs, or cells.

The present invention relates to a human artificial chromosome which is genetically transmissible to the next generation with high efficiency and the method for using the same. More specifically, the present invention relates to: a human artificial chromosome in which an about 3.5 Mb to about 1 Mb region containing an antibody light chain gene derived from human chromosome 22 is bound to a chromosome fragment which is transmissible to a progeny through a germ line of a non-human animal, said chromosome fragment is derived from another human chromosome; a non-human animal carrying the human artificial chromosome and an offspring thereof; a method for producing the non-human animal; a method for producing a human antibody using the nonhuman animal or an offspring thereof; and a human antibody-producing mouse carrying the human artificial chromosome.

The invention provides methods for reprogramming somatic cells to generate multipotent or pluripotent cells. Such methods are useful for a variety of purposes, including treating or preventing a medical condition in an individual. The invention further provides methods for identifying an agent that reprograms somatic cells to a less differentiated state.

Genetically modified mice are provided that express human variable (hV) sequences, including mice that express hV sequences from an endogenous mouse light chain locus, mice that express hV sequences from an endogenous mouse light chain locus, and mice that express hV sequences from a transgene or an episome wherein the hV sequence is linked to a mouse constant sequence. Mice are provided that are a source of somatically mutated human variable sequences useful for making antigen-binding proteins. Compositions and methods for making antigen-binding proteins that comprise human variable sequences, including human antibodies, are provided.