ULAM IN-VIVO ANIMAL CORE
UNIVERSITY OF MICHIGAN
Main Laboratory
North Campus Research Complex
2800 Plymouth Rd., Bld. 36: G155/157
Ann Arbor, MI 48109-2800
(734) 647-0731
North Campus Research Complex
2800 Plymouth Rd., Bld. 36: G155/157
Ann Arbor, MI 48109-2800
(734) 647-0731
Satellite Location
3527 Animal Research Facility
1150 W. Medical Center Dr.
Ann Arbor, MI 48109-0614
(734) 936-3803
3527 Animal Research Facility
1150 W. Medical Center Dr.
Ann Arbor, MI 48109-0614
(734) 936-3803
ulam-ivac@umich.edu
Case Information:
| Necropsy Date: | 12/20/23 | Clinician: | Lester/Martin |
|---|---|---|---|
| IVAC Service ID: | 23-3252 | Prosector: | Hasler |
| Species: | MUM | Gross necropsy pathologist: | Lee |
| Principal Investigator: | Lester/Wilcox | Other contact: | Michelle Drenth |
| Depart: | Breeding Colony |
Animal ID:
| Animal ID: | Clinical Number: | Age: | Sex: | Genotype/Strain/Study: | Mode of Death: |
|---|---|---|---|---|---|
| CLN00113835 | 3-7 months (unclear from cage card) | F | Rag2-, OT-1+, Sf/f, Cre- | Euthanized-CO2 |
Clinical History:
Nursing female mouse presented 12/13 with corneal ulceration and periorbital swelling of the left eye. Treatment with topical neo-poly-bac and flurbiprofen was initiated once a day. A recheck on 12/18 revealed significant swelling of the left side of the face, rendering the animal unable to open the eye fully. Lab reports that they have occasionally seen this in previous Rag2 KOs, but not for several months.
Final Diagnos(es) for Case
| Organ/System | Process | Diagnosis |
|---|---|---|
| Special senses | Infectious | Unilateral harderian gland abscess with gram-negative coccobacilli |
| Hematolymphoid | Inherited/Genetic | Lymphoproliferation, thymus and lymph nodes |
Final Comments:
Histopathology confirms a retroorbital abscess from the Harderian gland, with abundant intralesional gram-negative coccobacilli. Bacterial culture of the lesion confirmed positive for Rodentibacter heylii, which is a common pathogen for conjunctivitis, otitis, rhinitis, and cervical lymphadenitis in mice and rats. Immunocompromised mice infected with Rodentibacter heylii also develop retrobulbar abscess of the lacrimal glands/Harderian glands, which may be associated with penetrating foreign bodies. In this case, no bacteria or other infectious etiology was found in other organs. Robust lymphoid proliferation was noted in thymus and some lymph nodes, resembling T cell lymphoma, which has been reported as a background finding in OT-1 mice (Laffey et al., 2022). However, the lymphoid proliferation didn't seem to impact the animal clinically in the present case. Ref: Laffey KG, Stiles RJ, Ludescher MJ, et al. Early expression of mature αβ TCR in CD4-CD8- T cell progenitors enables MHC to drive development of T-ALL bearing NOTCH mutations. Proc Natl Acad Sci U S A. 2022 Jul 5;119(27):e2118529119. doi: 10.1073/pnas.2118529119. Epub 2022 Jun 29. PMID: 35767640; PMCID: PMC9271211.
Pathologist Only:
| Case Complete? | Yes |
|---|---|
| Final Review Pathologist: | Yao Lee, DVM, MS, PhD, DACVP |
| Completion Date: | 2024-01-17 |
Gross Findings
| Body condition score: | 3/5 |
|---|---|
| Carcass condition: | Intact |
| Autolysis: | None |
Gross Lesions
| Organ System | Evaluated? (Y/N/Some animals) | Findings or Comments Y/N | Comments (only if Findings) |
|---|---|---|---|
| Cardiovascular | Y | N | |
| Endocrine | Y | N | |
| Gastrointestinal | Y | N | |
| Hematolymphoid | Y | Y | Area of congestion at cranial pole of spleen. |
| Hepatic | Y | Y | Liver is slightly pale. |
| Integument | Y | N | |
| Musculoskeletal | Y | N | |
| Nervous | Y | N | |
| Reproductive | Y | N | |
| Respiratory | Y | N | |
| Special senses | Y | Y | Multilobulated, yellow, fluid-filled structure wrapping around dorsal and lateral aspects of the eye. Fluid inside is yellow with a creamy texture. |
| Urinary | Y | N |
Additional Procedures Performed: Check all that apply
| Tissues Frozen | Held back spleen, liver, and kidney. |
| Tissues Refrigerated | Swab of fluid from periorbital mass. |
| Culture, periorbital tissue | Moderate Rodentibacter heylii |
Microscopic Findings
| Organ/Slide | Findings Y/N | Description |
|---|---|---|
| Adrenal Glands | N | |
| Bladder | N | |
| Brain | N | |
| Eyes and optic nerves | N | |
| Heart | N | |
| Kidneys | N | |
| Liver | N | |
| Lungs | N | |
| Mammary Glands | N | |
| Mesenteric lymph nodes | Y | In multiple nodes, the parenchyma is largely infiltrated by sheets of neoplastic lymphocytes, which have the same morphology found in the thymus. |
| Skeletal muscle | N | |
| Skull | Y | On one side of the skull, the retroorbital area (Harderian gland and adjacent soft tissue) is replaced by a large abscess, consisting of lots of degenerate neutrophils mixed with colonies of gram-negative coccobacilli and cell debris, surrounded by fibrous connective tissue. This abscess compresses the skull, and there is a small portion of the bone being absent (osteolysis). The eye is displaced outward. |
| Spleen | Y | Decreased amount of lymphoid tissue (expected phenotype) |
| Sternum | Y | The bone marrow and a subcutaneous lymph node adjacent to it are infiltrated by large numbers of sheets of lymphocytes, with the same morphology found in the thymus. |
| Stomach and intestines | N | |
| Thymus | Y | The structure of cortex and medulla is obliterated by sheets of neoplastic lymphocytes. These cells are medium in size, with scant cytoplasm, round nucleus, prominent multiple nucleoli, and coarse chromatin. Apoptosis is frequent. Mitoses are 5 per high power field. |
| Uterus and ovaries | N |
Microscopic Morphologic Diagnos(es)
| Organ/System | Process | Morphologic Diagnosis |
|---|---|---|
| Harderian gland | Infectious | Abscess, locally extensive, severe, chronic active, with intralesional gram-negative coccobacilli, unilateral side of the skull |
| Thymus and multiple lymph nodes | Inherited/Genetic | Lymphoproliferation |