Rodent Preclinical Models for Developing Novel Antiarthritic Molecules: Comparative Biology and Preferred Methods for Evaluating Efficacy
Figure 5
Tissue trimming procedure for reliable and reproducible production of high-quality hind paw sections for histopathological analysis of immune-mediated arthritis in rodents. A skeletal schematic diagram (a) shows the location of the cuts required to isolate the tibiotarsal region. As viewed from the lateral side (a (left panel)), the hind paw is separated from the distal limb just above the tibiotarsal (hock (or “ankle”)) region at the fur line, and the digits (toes) are removed. From the top (a (right panel)), the hind paw is divided longitudinally using a cut placed between metatarsals II and III, which will fall just to the outside of the talus (the uppermost bone to the left of the orange line) and tibia (the distal leg bone (not shown)) that articulates with the talus. The distal tibia ((b), bracketed by forceps) is identified at the proximal cut margin of isolated hind paws as an oval white bone with a yellow/brown core of bone marrow. The longitudinal dividing cut (d) is made from the dorsal side by engaging the blade at the proximal and distal margins of the sample and then cutting straight down; the dashed black oval indicates the position of the tibia behind the razor blade, indicating that the blade is located just to the side of this bone. The microscopic structure of hind paw sections taken through this region from a nonarthritic rat (c) will include the joint spaces most susceptible to induced models of immune-mediated arthritis (asterisks (*)) as well as the most affected tarsal bones (navicular (N) and talus (Ta)), the distal tibia (Ti), and sometimes the calcaneus (C (or “heel”)). Histologic stain: hematoxylin and eosin (H&E).
