The Complete Mouse Phenotyping Service performs gross evaluation and histopathology on genetically altered mice. Findings are documented and presented in publication-ready format.
The Standard Phenotyping Panel
The following procedures comprise the phenotyping panel on each mouse:
- Gross necropsy, with whole mouse and major organ weights.
- Immersion fixation, followed by processing for hematoxylin-and-eosin histopathology. Tissues evaluated during the initial screen include:
- Head – nasal passages, teeth, skin, vomeronasal organ, eyes, inner, middle and outer ear, tongue, salivary glands, brain, pituitary gland, bone.
- Heart (longitudinal section), lung (wholelung), trachea and thyroid glands.
- Liver, gall bladder, adrenal glands and kidneys (in transverse and longitudinal section).
- Stomach, duodenum, jejunum, pancreas, mesenteric lymph nodes.
- Ileum, cecum and colon, rectum.
- Urinary bladder, testes, accessory sex glands, preputial gland (in males) or uterus, ovaries, clitoral gland and mammary gland (in females).
- Cervical lymphoglandular complex (cervical lymph node, submandibular, submaxillary and parotid lymph nodes), diaphragm.
- Hind and forelimbs and sternum (skeletal muscle, bone marrow, peripheral nerve, skin, joints)
- Blood smear
- Documentation of gross and microscopic lesions, and written report.
All blocks and slides are returned to the investigator.
Microbiology and Clinical Pathology: Additional tests can be requested at the time of necropsy. These include bacteriology, virology (performed in-house) and molecular diagnostics for infectious agents. Serum chemistry, complete blood count and urinalysis are performed by an outside company, Antech Diagnostics (1-800–872-1001). These samples may be submitted directly by the investigator.
In general, two age-matched mice of each gender and of each genotype (–/–, +/– and +/+) are the minimum number of animals that can be submitted in order to obtain meaningful data. The age at which mice are submitted depends upon the age at which the phenotype becomes apparent – if there is no clinical phenotype, submitting a set of young (6-8 weeks) and older (15-20 months) animals is recommended.
Issues impacting successful anatomic phenotyping: Numerous variables impact interpretation of pathology in mice. These include background strain, extent of backcrossing, disease status, and information about the manipulated gene, or experimental therapy. These should be considered prior to designing a study. Key references reviewing these are provided below:
Kilkenny CL, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010 June 29;8(6):e1000412.
Brayton CF, Treuting PM, Ward JM. Pathology of aging mice and GEM: background strains and experimental design. Vet Pathol. 2012 Jan;49(1):85-105.
Zeiss CJ, Ward JM, Allore HG. Designing phenotyping studies for genetically engineered mice. Vet Pathol. 2012 Jan;49(1):24-31.
Caroline Zeiss, BVSc, Dip. ACVP & ACLAM, Ph.D.
Carmen Booth, D.V.M., Ph.D.