Non-human animals comprising a human or humanized DPP4 nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous Dpp4 gene with a human or humanized DPP4 gene, or non-human animals comprising a human or humanized DPP4 gene in addition to the endogenous Dpp4 gene are described. Non-human animals comprising a human or humanized DPP4 gene under control of human or non-human DPP4 regulatory elements is also provided, including non-human animals that have a replacement of non-human Dpp4-encoding sequence with human DPP4-encoding sequence at an endogenous non-human Dpp4 locus. Non-human animals comprising human or humanized DPP4 gene sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided. Methods for making and using the non-human animals are described.

Non-human animals comprising a human or humanized DPP4 nucleic acid sequence are provided. Non-human animals that comprise a replacement of the endogenous Dpp4 gene with a human or humanized DPP4 gene, or non-human animals comprising a human or humanized DPP4 gene in addition to the endogenous Dpp4 gene are described. Non-human animals comprising a human or humanized DPP4 gene under control of human or non-human DPP4 regulatory elements is also provided, including non-human animals that have a replacement of non-human Dpp4-encoding sequence with human DPP4-encoding sequence at an endogenous non-human Dpp4 locus. Non-human animals comprising human or humanized DPP4 gene sequences, wherein the non-human animals are rodents, e.g., mice or rats, are provided. Methods for making and using the non-human animals are described.

An object of the present invention is to provide a fluorescent probe that can be used in an enzyme activity detection method. According to the present invention, there is provided a fluorescent probe for detecting a hydrolase, the fluorescent probe containing a compound having at least one water-soluble substituent selected from the group consisting of CO.sub.2H, PO.sub.3H.sub.2, and SO.sub.3H and represented by General Formula (II), or a salt thereof. The fluorescent probe of the present invention can be used in an enzyme activity detection method using a microdevice.

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The present invention relates to novel tetravalent multispecific antibodies, their manufacture and use.

Fibroblast activation protein a (FAP) is a tumor-specific protein and well characterized for its function in tumorigenicity. However, agents against its enzymatic activity or monoclonal antibodies against its cell surface presence are unsuccessful in clinic for uncharacterized reason. In this disclosure, provided is an anti-FAP siRNA and FAP-silencing oligonucleotides comprising anti-FAP siRNAs linked at both ends to aptamers recognizing cancer markers, in particular aptamers recognizing epithelial cell adhesion molecule (EpCAM).