The present invention includes compositions and methods for treating diseases or disorders associated with pathological calcification or pathological ossification. In certain embodiments, the diseases or disorders are selected from the group consisting of Generalized Arterial Calcification of Infancy (GACI), Idiopathic Infantile Arterial Calcification (IIAC), Ossification of the Posterior Longitudinal Ligament (OPLL), hypophosphatemic rickets, osteoarthritis, calcification of atherosclerotic plaques, PXE, hereditary and non-hereditary forms of osteoarthritis, ankylosing spondylitis, hardening of the arteries occurring with aging, calciphylaxis resulting from end stage renal disease and progeria.

Provided herein, in some aspects, is a NOD.Cg-Prkdc.sup.scid Il2rg.sup.tm1wjl/SzJ (NOD scid gamma or NSG™) mouse comprising a nucleic acid encoding human FLT3L and an inactivated mouse Flt3 allele, methods of producing the mouse, and methods of using the mouse.

The invention described herein provides non-HLA matched humanized mouse model (e.g., NSG mouse model) with patient-derived xenograft (PDX), as well as methods of making and using the same.

The present disclosure relates to methods and compositions for modulating immune responses, methods of treating or preventing diseases such as autoimmune and inflammatory disorders and cancer, as well as methods of enhancing immune responses to antigens and for the treatment of infectious diseases.

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.

Disclosed are means, methods and compositions of matter useful for treatment of inflammatory and/or viral mediated disease through administration of cellular populations subsequent to modulation of complement pathway. In one embodiment, patients with COVID-19 who are eligible for stem cell therapy are pretreated with modulators of complement activity in order to reduce inflammation and to augment activity of said stem cell therapy. Activity of said stem cell therapy includes protection of pulmonary cells from dysfunction/death, stimulation of regenerative/trophic activities, reduction of inflammation, and induction of immune modulation.

Genetically modified non-human animals and methods and compositions for making and using them are provided, wherein the genetic modification comprises a deletion of the endogenous low affinity FcγR locus, and wherein the mouse is capable of expressing a functional FcRγ-chain. Genetically modified mice are described, including mice that express low affinity human FcγR genes from the endogenous FcγR locus, and wherein the mice comprise a functional FcRγ-chain. Genetically modified mice that express up to five low affinity human FcγR genes on accessory cells of the host immune system are provided.

A mouse with a humanization of the mIL-3 gene and the mGM-CSF gene, a knockout of a mRAG gene, and a knockout of a mIl2rg subunit gene; and optionally a humanization of the TPO gene is described. A RAG/Il2rg KO/hTPO knock-in mouse is described. A mouse engrafted with human hematopoietic stem cells (HSCs) that maintains a human immune cell (HIC) population derived from the HSCs and that is infectable by a human pathogen, e.g., S. typhi or M. tuberculosis is described. A mouse that models a human pathogen infection that is poorly modeled in mice is described, e.g., a mouse that models a human mycobacterial infection, wherein the mouse develops one or more granulomas comprising human immune cells. A mouse that comprises a human hematopoietic malignancy that originates from an early human hematopoietic cells is described, e.g., a myeloid leukemia or a myeloproliferative neoplasia.

The present disclosure relates to genetically modified non-human animals that express a human or chimeric (e.g., humanized) IL4R and/or IL4, and methods of use thereof.

An atopic dermatitis model non-human animal, containing a gene mutation in which a complex containing dedicator of cytokinesis 8 (DOCK8) protein, mammalian STE20-like kinase 1 (MST1) protein, and endothelial PAS domain protein 1 (EPAS1) protein is not formed in CD4.sup.+ T cells.