The Standard Phenotype

A minimum of two mice, a genetically engineered animal and an appropriate (i.e., sex-, age-, and stain-matched) control mouse, are required. The mice are euthanized by carbon dioxide inyhalation, weighed, and blood obtained for subsequent hematology (CBC with differential) and clinical pathology (16 routine assays). Comparative survey radiographs are taken with the animals in ventral and lateral recumbancy.

A complete necropsy is performed. All organs are examined grossly, and the following organs are routinely weighed to the nearest milligram prior to fixation for determining organ-to-body weight ratios (% b. wt.):

• liver
• spleen
• kidneys (both)
• adrenals (both)
• heart
• interscapular brown fat
• brain (intact, with olfactory lobes)
• pituitary

Any other organ(s) can be weighed upon request.

The following tissues are fixed in 10% neutral buffered formalin for histologic examination:

• peripheral lymph nodes
• heart
• thymus
• diaphragm
• tongue
• skeletal muscle (soleus and hamstrings, abdominal wall with peritoneum)
• lungs
• trachea with thyroid/parathyroids
• kidneys
• adrenals
• ureters
• submandibular and parotid salivary glands with lymph nodes
• stomach
• entire GI tract through the anus
• mesenteric lymph nodes
• entire liver
• spleen
• pancrease
• urinary bladder
• uterus, ovaries, vagina, and clitoral glands, or
• testes with epididymes, vas deferens, seminal vesicles, prostrate, bulbourethral and perputial glands
• dorsal and ventral skin (shaved)
• mammary glands
• brain
• pituitary
• eyes
• skull
• skeleton
• spinal cord (within column)
• any grossly apparent lesions

All bony tissues are decalcified prior to trimming and preserved tissues are trimmed according to a standardized protocol. Trimmed tissues are embedded in paraffin, sectioned at 4 um, and routinely stained with hematoxylin and eosin. Most cases will generate 19 H&E slides/mouse. Microsopic evaluation is performed by a member of the American College of Veterinary Pathologists or by a veterinary pathology trainee under the supervision of a member of the American College of Veterinary Pathologists. All wet tissues remaining are held for the PI and returned with the finished slides and blocks, along with a hard copy of the final report.

A preliminary report is generated after the gross necropsy and includes the results of blood work as well as any gross photos taken. The final written report for each set of genetically altered and control mice includes the preliminary report to which the pathologist's descriptions of microscopic lesions observed, the survey radiographs, and any electronic images of gross and significant microscopic lesions discovered have been added. The final also includes an interpretive summary of the findings and recommendations for additional studies.