Non-human animals, and methods and compositions for making and using the same, are provided, wherein said non-human animals comprise a humanization of an Angiopoietin-like protein 8 (ANGPTL8) gene. Said non-human animals may be described, in some embodiments, as having a genetic modification to an endogenous ANGPTL8 locus so that said non-human animals express a human ANGPTL8 polypeptide.

A genetically modified non-human animal comprising a genome containing an endogenous non-human ACE2 locus genetically modified to encode a complete human ACE2 gene. According to a further embodiment the genome is genetically modified to encode a second, a third, and a fourth complete human ACE2 gene, the human ACE2 gene is at least 85 percent identical to SEQ ID No: 1, the animal of is a mouse, the human ACE2 gene encodes six protein variants, an endogenous Tmprss2 gene is unmodified, a LoxP gene flanks each of a 5′ and a 3′ end of a nucleic acid sequence of the human ACE2 gene, and the human ACE2 gene is expressed in a lung, kidney, spleen, stomach, liver, intestine, heart, and skeletal muscle of the animal, and a cortex, striatum, middle brain, hippocampus, olfactory bulb, and cerebellum of a brain of the animal.

Recurrent gene fusions of androgen regulated genes and ETS family member genes in prostate cancer are described. Compositions and methods having utility in prostate cancer diagnosis, research, and therapy are also provided.

The present invention provides a method of bioluminescence-driven optogenetic control of excitable cells. The excitable cell expresses a light-gated ion channel, and a luminescent protein can be expressed either in the excitable cell or in another cell proximal to the excitable cell. The methods of the invention can be used to desynchronize local activity of excitable cells in a mammalian tissue. The methods of the invention can be used to treat a disease or condition in a mammal, the disease or condition being related to bursting. The disease or condition can be Parkinson's disease, epilepsy, a sleep disorder, or a sensory-related disease or condition (e.g., attention deficit disorder or pain). The invention also provides a conjugate of containing a voltage-gated ion channel and a luminescent protein.

The present invention relates to a porcine alpha-S1-casein gene, a porcine alpha-S1-casein gene promoter, an expression comprising the same promoter, and a method for the production of a target protein using the same expression vector. The promoter of the present invention facilitates the mammary gland-specific expression of the target protein. Accordingly, an animal transformed with the promoter secretes the target protein in milk at high concentration, and thus can be advantageously used for the production of useful proteins.

The invention provides compositions and methods useful for the treatment and prevention of conditions associated with short telomere length.

Compositions and methods are provided for measuring population size for a plurality of clonal cell populations in the same individual, e.g., for measuring tumor size for a plurality of clonally independent tumors within the same individual. A subject method can include: (a) contacting an individual with a plurality of cell markers that are heritable and distinguishable from one another, to generate a plurality of distinguishable lineages of heritably marked cells; (b) after sufficient time has passed for the heritably marked cells to undergo at least one round of division, detecting and measuring quantities of at least two of the plurality of cell markers present in the contacted tissue, thereby generating a set of measured values: and (c) using the set of measured values to calculate the number of heritably marked cells that are present (e.g., for at least two of the distinguishable lineages of heritably marked cells).

The skin is one of first lines of defense against external threats. Tissue-resident macrophages have pivotal functions in tissue-barrier integrity and homeostasis. Upon skin inflammation, a functional crosstalk between the sensory nervous system and tissue-resident immune cells can regulate cutaneous immune responses. However, depending on the pathological context, sensory neurons display pro- or anti-inflammatory regulatory properties. Here the inventors identify, in a model of ultraviolet (UV)-induced skin N damage, a regulatory role for type C low-threshold mechanoreceptor (C-LTMR) sensory neurons on the dynamic of dermal macrophage replacement by inflammatory monocytes through the neuropeptide TAFA4. Tafa4-KO mice present an unresolved fibrotic dermis after UV irradiation. Increased fibrotic score correlates with the upstream persistency of inflammatory monocytes and their MHC-II.sup.+ macrophage progeny. Bone marrow chimera revealed that inflammatory monocyte differentiation towards CD206+ dermal macrophage is increased in Tafa4KO recipient. Finally, intradermal injection of TAFA4 at the site of UV irradiation reduces inflammatory monocytes accumulation and skin inflammation in Tafa4-KO mice. The results provide new insight about tissue-resident macrophages dynamic during the resolution of skin fibrosis and thus renders credible the use of TAFA4 for the treatment of skin inflammation.

Described herein are donor vectors and systems for use in dual recombinase-mediated cassette exchange. Also described herein are animal models and human cells for consistent, rigorous, and facile investigation of transgene expression. Further described herein are methods of screening for therapeutic drugs using these animal models, and methods of treatment.

Provided herein is a method of suppressing osteoclast differentiation or function and/or bone resorption or destruction in a subject in need thereof and compositions therefore. In one embodiment, the method includes increasing the amount, expression, or activity of Foxo3 isoform 2 in the subject.