The present invention relates to dispensing instruments and methods for introducing treatment material and fluid-like material with an embryo into a uterus. More specifically, the present invention relates to apparatuses for delivering a fertilized egg or embryo into a maternal uterine endometrium in humans or any other mammalian species and associated computer programs for controlling said apparatuses.

An embryo transfer tool has a flexible tube and a hub. The flexible tube has first and second microparticle-containing synthetic resin portions. The first and second microparticle-containing synthetic resin portions are not exposed in outer and inner surfaces of the flexible tube, and are formed by a synthetic resin and a large number of hollow glass beads having a diameter of 0.5 to 200 μm. The hollow glass beads are dispersed in the synthetic resin. The first and second microparticle-containing synthetic resin portions include a large number of boundary surfaces that are formed between the synthetic resin and the hollow glass beads.

Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.

Compositions and methods are provided for modifying a rat genomic locus of interest using a large targeting vector (LTVEC) comprising various endogenous or exogenous nucleic acid sequences as described herein. Compositions and methods for generating a genetically modified rat comprising one or more targeted genetic modifications in their germline are also provided. Compositions and methods are provided which comprise a genetically modified rat or rat cell comprising a targeted genetic modification in the rat interleukin-2 receptor gamma locus, the rat ApoE locus, the rat Rag2 locus, the rat Rag1 locus and/or the rat Rag2/Rag1 locus. The various methods and compositions provided herein allows for these modified loci to be transmitted through the germline.

The invention relates to an oocyte-holding pipette for sperm injection methods without cytoplasmic aspiration, comprising an elongate, narrow, hollow, cylindrical body, inside which runs a suction conduit that communicates with a working end in order to hold an oocyte, said working end being flared to form a funnel defining an internal conical cavity, the proximal end of which, of smaller diameter, communicates with the suction conduit and the distal end of which, of larger diameter, is dimensioned to receive the oocyte in a tight-fitting manner, such that, upon aspirating same via the suction conduit, the oocyte remains partially trapped inside and becomes deformed, changing from its spherical shape in the resting state to an oval shape that tensions the surface and increases the turgor.

An apparatus for micromanipulation of biological material, includes a vessel (1) having a reservoir (2) wherein the vessel has a channel (3) formed in a portion of the reservoir, the channel including an intermediate restriction (4) dimensioned to resist passage of the biological material but allow passage of liquid treatment solutions.

An apparatus for micromanipulation of biological material, includes a vessel (1) having a reservoir (2) wherein the vessel has a channel (3) formed in a portion of the reservoir, the channel including an intermediate restriction (4) dimensioned to resist passage of the biological material but allow passage of liquid treatment solutions.

Methods of creating mutations in genomic exons by inserting introns into the genomic exons via homologous recombination. Also, methods are provided for introducing modifications into genomic exons by inserting introns into the genomic exons via homologous recombination such that a mature mRNA transcript produced from a genomic region of the genome comprising the genomic exon does not contain the modification are provided. The methods provide for a rapid method for introducing mutations and/or modifications of any type into a mammalian cell genome.

Methods of creating mutations in genomic exons by inserting introns into the genomic exons via homologous recombination. Also, methods are provided for introducing modifications into genomic exons by inserting introns into the genomic exons via homologous recombination such that a mature mRNA transcript produced from a genomic region of the genome comprising the genomic exon does not contain the modification are provided. The methods provide for a rapid method for introducing mutations and/or modifications of any type into a mammalian cell genome.

Compositions and methods are provided for making rat pluripotent and totipotent cells, including rat embryonic stem (ES) cells. Compositions and methods for improving efficiency or frequency of germline transmission of genetic modifications in rats are provided. Such methods and compositions comprise an in vitro culture comprising a feeder cell layer and a population of rat ES cells or a rat ES cell line, wherein the in vitro culture conditions maintain pluripotency of the ES cell and comprises a media having mouse leukemia inhibitory factor (LIF) or an active variant or fragment thereof. Various methods of establishing such rat ES cell lines are further provided. Methods of selecting genetically modified rat ES cells are also provided, along with various methods to generate a transgenic rat from the genetically modified rat ES cells provided herein. Various kits and articles of manufacture are further provided.