The present invention describes transgenic animals with human(ized) immunoglobulin loci and transgenes encoding human(ized) Ig and/or Ig sequences. Of particular interest are animals with transgenic heavy and light chain immunoglobulin loci capable of producing a diversified human(ized) antibody repertoire that have their endogenous production of Ig and/or endogenous Ig and/or Ig sequences suppressed. Simultaneous expression of human(ized) immunoglobulin and human(ized) Ig and/or Ig results in normal B-cell development, affinity maturation and efficient expression of human(ized) antibodies.

The invention relates to a long DH (LDH) cassette comprising a recombinant DH construct comprising at least two DH gene segments encoding at least 10 amino acids of the HCDR3 amino acid sequence, wherein at least one of the DH gene segments is a heterologous DH gene segment; an immunoglobulin heavy chain locus and a transgenic non-human animal comprising the same; and their use in producing an immunoglobulin library with long HCDR3 regions.

The present invention concerns non-human animals with cells having a genome that is lacking the entire E3 ubiquitin ligase (Ube3a) gene (including all isoforms and alternative promoters). These animals are useful for modeling Angelman Syndrome. The invention also includes methods for assessing the effect of an agent, such as potential therapeutics, on an animal model by exposing the animal or cells, tissues, or organs isolated therefrom, to an agent of interest.

A mutated Csf1r gene is disclosed. The mutated Csf1r gene is obtained by changing the 2557th nucleotide of a Csf1r gene from C to A, leading to obtain a mutated protein encoded by the mutated Csf1r gene substitute the 853rd amino acid from proline to threonine. The mutated protein, expression vectors, recombinant viruses, recombinant cells, recombinant bacteria, or recombinant vectors are also disclosed. A method for constructing a murine model with mutations in Csf1r gene. This method includes introducing the targeted vector containing the mutated Csf1r gene into mouse embryonic stem cells, followed by injection into blastocysts to generate F0 generation mice. The F0 generation mice are then bred with mice that specifically express Cre enzyme in tissues, followed by screening. The constructed murine model has significant applications in studying the pathogenic mechanisms of brain diseases caused by microglial cell dysfunction and screening valuable medicine for treating brain diseases.

Genetically modified non-human animals and methods and compositions for making and using the same are provided, wherein the genetic modification comprises a humanization of an endogenous signal-regulatory protein gene, in particular a humanization of a SIRP? gene. Genetically modified mice are described, including mice that express a human or humanized SIRP? protein from an endogenous SIRP? locus.

The invention relates to a long DH (LDH) cassette comprising a recombinant DH construct comprising at least two DH gene segments encoding at least 10 amino acids of the HCDR3 amino acid sequence, wherein at least one of the DH gene segments is a heterologous DH gene segment; an immunoglobulin heavy chain locus and a transgenic non-human animal comprising the same; and their use in producing an immunoglobulin library with long HCDR3 regions.

Disclosed herein are nucleic acids encoding for and proteins expressing chimeric C1q polypeptides, non-human animals comprising said nucleic acids, and methods of making or using said non-human animals.

A transgenic knockout non-human animal is described whose genome includes a heterozygous disruption of the expression of at least one endogenous gene encoding zinc-finger, CCHC domain-containing protein 6 (ZCCHC6). The transgenic animal model can be used to study bone disease or development by determining differences in bone characteristics, protein expression, or cytokine expression in the animal model in comparison to a corresponding wild-type non-human animal.

A genetic element including a splice donor site, a first recombinase recognition site, a splice branch point, a second recombinase recognition site, a splice acceptor site, wherein the splice branch point is at a distance of 10 to 56 nucleotides in length from the splice acceptor site, and its uses in controlled gene inactivation in a cell is disclosed.

Disclosed herein are methods and compositions for genome editing of one or more loci in a rat, using fusion proteins comprising a zinc-finger protein and a cleavage domain or cleavage half-domain. Polynucleotides encoding said fusion proteins are also provided, as are cells comprising said polynucleotides and fusion proteins.