Jodi A Carlson Scholz

Kcnn4 is a regulator of macrophage multinucleation in bone homeostasis and inflammatory disease.

Summary Macrophages can fuse to form osteoclasts in bone or multinucleate giant cells (MGCs) as part of the immune response. We use a systems genetics approach in rat macrophages to unravel their genetic determinants of multinucleation and investigate their role in both bone homeostasis and inflammatory disease. We identify a trans-regulated gene network associated with macrophage multinucleation and Kcnn4 as being the most significantly trans-regulated gene in the network and induced at the onset of fusion. Kcnn4 is required for osteoclast and MGC formation in rodents and humans. Genetic deletion of Kcnn4 reduces macrophage multinucleation through modulation of Ca2+ signaling, increases bone mass, and improves clinical outcome in arthritis. Pharmacological blockade of Kcnn4 reduces experimental glomerulonephritis. Our data implicate Kcnn4 in macrophage multinucleation, identifying it as a potential therapeutic target for inhibition of bone resorption and chronic inflammation.

Additive Effects of Mechanical Marrow Ablation and PTH Treatment on de Novo Bone Formation in Mature Adult Rats.

Mechanical ablation of bone marrow in young rats induces rapid but transient bone growth, which can be enhanced and maintained for three weeks by the administration of parathyroid hormone (PTH). Additionally, marrow ablation, followed by PTH treatment for three months leads to increased cortical thickness. In this study, we sought to determine whether PTH enhances bone formation after marrow ablation in aged rats. Aged rats underwent unilateral femoral marrow ablation and treatment with PTH or vehicle for four weeks. Both femurs from each rat were analyzed by X-ray and pQCT, then analyzed either by microCT, histology or biomechanical testing. Marrow ablation alone induced transient bone formation of low abundance that persisted over four weeks, while marrow ablation followed by PTH induced bone formation of high abundance that also persisted over four weeks. Our data confirms that the osteo-inducive effect of marrow ablation and the additive effect of marrow ablation, followed by PTH, occurs in aged rats. Our observations open new avenues of investigations in the field of tissue regeneration. Local marrow ablation, in conjunction with an anabolic agent, might provide a new platform for rapid site-directed bone growth in areas of high bone loss, such as in the hip and wrist, which are subject to fracture.

Care of Mastomys in the laboratory.

Mastomys rodents occupy a valuable niche in biomedical research, but there is very little published information regarding how to care for them in the laboratory. Here we provide information about the physical and behavioral characteristics of this unusual laboratory rodent, its taxonomic history, common diseases that affect it, and its use in research. We also provide housing recommendations based upon almost 15 years of experience successfully maintaining a colony of Mastomys coucha at our institution.

Deer Mice, White-Footed Mice, and their Relatives

Publisher Summary Peromyscus are myomorph rodents belonging to the family of Cricetidae and to the subfamily Neotominae. Neotominae comprises 16 genera of New World cricetid rodents including deer mice, woodrats, and their relatives. The white-footed mouse is the most commonly used in research. This chapter primarily describes the physical attributes, geographical habitat, lifespan, and uses in research of deer mice and white footed-mice. The chapter studies the infectious, bacterial, and viral diseases of deer mice. Despite their common names, deer mice and white-footed mice are not closely related to common laboratory mice of the genus Mus, or to laboratory rats (Rattus). Several inhalant and injectable anesthetic regimens have been used successfully in Peromyscus.