Provided is a method for preparing a PD-1 gene-modified humanized animal model. The method utilizes the CRIPSR/Cas9 technique to replace partial fragments of a mouse PD-1 gene with fragments of a human PD-1 gene using homologous recombination by constructing a targeting vector, thereby preparing a gene-modified humanized mouse. This mouse can normally express a PD-1 protein containing the functional domain of the human PD-1 protein, and can be used as an animal model for mechanism research regarding PD-1, PD-L1 and other signals, for screening regulators, and for toxicological research. The method has an important and high application value in studies on functions of the PD-1 gene and in the development of new drugs.

Provided are ex vivo and in vivo methods utilizing therapeutic genes for treatment of male and female infertility, including non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) and comorbid diseases, with or without transmitting the therapeutic gene to offspring of the infertile subject. Germline gene therapy methods are also described to reduce or eliminate disease from families with or without transmission of the therapeutic gene to offspring.

Provided are ex vivo and in vivo methods utilizing therapeutic genes for treatment of male and female infertility, including non-obstructive azoospermia (NOA) and premature ovarian insufficiency (POI) and comorbid diseases, with or without transmitting the therapeutic gene to offspring of the infertile subject. Germline gene therapy methods are also described to reduce or eliminate disease from families with or without transmission of the therapeutic gene to offspring.

The invention encompasses improved catheters comprised of multiple tubular bodies and methods of using them in artificial insemination.

The present invention relates to a method for increasing the embryo implantation rate in a mammalian uterus, by administering to the uterus of a mammal an effective amount of an extracellular matrix remodeling enzyme, as well as to a product comprising an extracellular remodeling enzyme.

The present invention relates to a method for increasing the embryo implantation rate in a mammalian uterus, by administering to the uterus of a mammal an effective amount of an extracellular matrix remodeling enzyme, as well as to a product comprising an extracellular remodeling enzyme.

Applicants have identified that three critical phenotypic/genetic measures are highly correlated with transition period health and may be used in selection and breeding protocols and/or in combination with traditional breeding and marker assisted selection methods to improve predictability of transition period health. According to the invention genetic evaluations for mastitis, ketosis, and metritis have been found to be highly predictive of overall transition health. The genetic evaluations are produced by directly measuring thousands of clinical cases of mastitis, ketosis, and metritis in ancestors of a particular animal and using this data in selection. Applicant's selection criteria and quickly impact a breeders population by reducing transition cow disease incidence in the initial population and in progeny.

Applicants have identified that three critical phenotypic/genetic measures are highly correlated with transition period health and may be used in selection and breeding protocols and/or in combination with traditional breeding and marker assisted selection methods to improve predictability of transition period health. According to the invention genetic evaluations for mastitis, ketosis, and metritis have been found to be highly predictive of overall transition health. The genetic evaluations are produced by directly measuring thousands of clinical cases of mastitis, ketosis, and metritis in ancestors of a particular animal and using this data in selection. Applicant's selection criteria and quickly impact a breeders population by reducing transition cow disease incidence in the initial population and in progeny.

The present invention is drawn to novel methods of selecting mammals receptive to embryo transfers in order to improve reproductive efficiency and milk production of the mammals. The present invention encompasses three methods: (1) selecting from any group of mammals; (2) selecting from estrus-negative mammals; and (3) selecting from estrus-negative mammals and pooling the selected mammals with estrus-positive mammals. Also encompassed is a kit for selecting mammals receptive to embryo transfers.

Provided is a method for preparing a PD-1 gene-modified humanized animal model. The method utilizes the CRIPSR/Cas9 technique to replace partial fragments of a mouse PD-1 gene with fragments of a human PD-1 gene using homologous recombination by constructing a targeting vector, thereby preparing a gene-modified humanized mouse. This mouse can normally express a PD-1 protein containing the functional domain of the human PD-1 protein, and can be used as an animal model for mechanism research regarding PD-1, PD-L1 and other signals, for screening regulators, and for toxicological research. The method has an important and high application value in studies on functions of the PD-1 gene and in the development of new drugs.