Whole mouse phenotyping
Carmen Jane Booth, DVM, PhD
Director of Comparative Pathology ResearchAbout the service
Phenotyping of whole mice involves a complete macroscopic (gross) and histopathologic (microscopic) evaluation on genetically altered mice. Findings are documented and presented in publication-ready format.
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 (whole lung), 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.
Available to Yale researchers & external researchers
Fixation protocols
Immersion & perfusion fixationGetting started
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.
Key references
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 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.
Rates
The Mouse Research Pathology Service is the only service at the Yale School of Medicine providing pathologic phenotyping by comparative veterinary pathologists. In addition to gross and histologic evaluation of animal models, we also provide a variety of high quality histology services tailored to individual projects.
Rates effective 1/1/25
| Services | Unit | Yale research investigator | External research investigator |
|---|---|---|---|
| C&T technical time | per hour | $79.50 | $119.72 |
| M&P technical time | per hour | $79.00 | $115.00 |
| Pathologist | per hour | $140.00 | $204.50 |
| Necropsy: Research--rodent (supplies only) | per necropsy | $5.00 | $116.00 |
| Histology: Tissue processing only | per sample | $10.00 | $0 |
| Histology: Tissue processing and embedding | per sample | $12.25 | $35.00 |
| Histology: Tissue processing, embedding, sectioning, 1st H&E slide | per sample | $21.00 | $65.50 |
| Histology: Cut unstained section from block (1-2 sections on one slide) | per slide | $3.50 | $14.75 |
| Histology: H&E slide | per slide | $5.25 | $69.00 |
| Histology: Special stains, non-silver stain only; no sectioning | per slide | $11.75 | $45.00 |
| Histology: Silver stain only; no sectioning | per slide | $21.00 | $83.00 |
| Histology: Frozen sectioning | per section | $21.00 | $400.00 |
| Microbiology: Aerobic culture, including Pseudomonas screening culture, urine cultures, cecal screening culture | per sample | $88.00 | $0 |
| Microbiology: Anaerobic culture | per sample | $130.00 | $0 |
| Microbiology: Antibiotic sensitivity--group 1 | per sample | $84.00 | $0 |
| Microbiology: Antibiotic sensitivity--group 2 | per sample | $84.00 | $0 |
| Microbiology: Blood culture | per sample | $145.00 | $0 |
| Microbiology: Diff Quik stain | per sample | $34.00 | $0 |