Comprehensive Cancer Center
Department of Veterinary Biosciences
1900 Coffey Road
467/471 Veterinary Medicine Academic Building
Columbus, OH 43210
Phone: 614.247.8122
Accession #: 2013-2-219
Institution: OSU-CCC
PI Name: Harper
ULAR #: Not applicable
email: CPMPSR@cvm.osu.edu
Key:
Black underline = AAV.miLacZ injected
Yellow highlight = AAV.miMYOT injected
Mice 1-14 = TgT57I
Mice 14-28 = WT
Fax: 614.292.6473
Service: Research
Housing Location: Children s
Submitter: Liu, Jian
Room #: WA4106
Phone/Pager #:
Veterinarian: Not provided
Email:
Date Received: 2/28/2013
Protocol #: AR11-00024
Mice 1-8 (2027, 1968, 1868, 1869, 1969, 2160, 2161 and 2162) and Mice 9-14 (2179, 2180, 2205, 2436, 1964 and 1965)
are MYOT mice. Although additional information was not provided, it is assumed these are transgenic for the human
myotilin gene under control of the human skeletal muscle alpha 1 actin promoter. These mice have no reported
phenotype.
Mice 15-22 (2406, 1876, 1899, 1903, 1872, 1874, 1875 and 1870) and Mice 23-28 (1967, 2159, 2207, 2435, 2437 and
2206) are wildtype mice. It was not indicated whether these mice are littermate genotype controls of the MYOT mice
above.
Mice 1-8 (2027, 1968, 1868, 1869, 1969, 2160, 2161 and 2162) and Mice 15-22 (2406, 1876, 1899, 1903, 1872, 1874,
1875 and 1870) were noted to be "injected" mice; however, no details regarding what was injected were provided.
The birthdate (12/1/11) of the mice was provided; however, the date of death was not.
Patient No: 1
ID #: 2027
Species: Mouse
Tests Ordered:
GEM: Yes
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Diaphragm (3 sections; slide 1): No significant microscopic lesions (NSML).
Testis (slide 2): Seminiferous tubular degeneration and atrophy, multifocal (-5 tubules), mild.
Spleen, heart and lung (slide 2): NSML.
Kidney (slide 2): There are multifocal, small aggregates of lymphocytes and plasma cells in the interstitium, particularly
in the pelvis. Lumens of few (presumptive) distal tubules multifocally within the cortex are mildly ectatic and lined by low
columnar epithelial cells.
Liver (slide 2): Hepatocellular vacuolar change consistent with lipidosis, microvacuolar to macrovacuolar, centrilobular to
midzonal, widespread, moderate.
Patient No: 2
ID #: 1968
Accession # 2013-2-219
GEM: Yes
Construct:
Tests Ordered:
Slide Evaluation
Page 1
Comparative Pathology & Mouse
Phenotyping Shared Resource
Species: Mouse
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Diaphragm (slide 1): NSML.
Testis, heart, lung and kidney (slide 2): NSML.
Spleen (slide 2): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Liver (slide 2): Hepatocellular vacuolar change consistent with glycogen, widespread, moderate with multifocal random
areas of hepatocellular microvacuolar lipidosis.
Patient No: 3
ID #: 1868
Species: Mouse
Tests Ordered:
GEM: Yes
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Testis, heart, lung and liver (slide 3): NSML.
Spleen (slide 3): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Kidney (slide 3): Lumens of (presumptive) distal tubules throughout the cortex are moderately ectatic and lined by low
columnar epithelial cells. There are multifocal small aggregates of lymphocytes and plasma cells in the interstitium,
particularly in the pelvis. In addition there is a focal, mild, subcapsular area of tubular regeneration.
Diaphragm (slide 4): NSML.
Patient No: 4
ID #: 1869
Species: Mouse
Tests Ordered:
GEM: Yes
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart and lung (slide 5): NSML.
Spleen (slide 5): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Kidney (slide 5): Lumens of (presumptive) distal tubules throughout the cortex are moderately ectatic and lined by low
columnar epithelial cells.
Testis (slide 5): Seminiferous tubular degeneration and atrophy, multifocal (-3 tubules), mild.
Liver (slide 5): Hepatocellular vacuolar change consistent with microvacuolar and macrovacuolar hepatocellular lipidosis,
multifocal, random, mild with multifocal ito cell hyperplasia.
Diaphragm (slide 6): NSML.
Accession # 2013-2-219
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Phenotyping Shared Resource
Patient No: 5
ID #: 1969
Species: Mouse
Tests Ordered:
GEM: Yes
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart and lung (slide 1): NSML.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Testis (slide 1): Seminiferous tubular degeneration and atrophy, multifocal (-5 tubules), mild.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, moderate with multifocal random
areas of hepatocellular microvacuolar lipidosis.
Kidney (slide 1): Lumens of few (presumptive) distal tubules multifocally distributed in the cortex are mildly ectatic and
lined by low columnar epithelial cells.
Diaphragm (slide 2): NSML.
Patient No: 6
ID #: 2160
Species: Mouse
Tests Ordered:
GEM: Yes
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart, lung, kidney and testis (slide 1): NSML.
Liver (slide 1): Hepatocellular hypertrophy, centrilobular to midzonal, widespread, mild.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Diaphragm (slide 2): NSML.
Patient No: 7
ID #: 2161
Species: Mouse
Tests Ordered:
GEM: Yes
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart and lung (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widepread, mild.
Spleen (2 sections; slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal
centers.
Kidney (slide 1): There is a focal area of mild tubular regeneration.
Accession # 2013-2-219
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Phenotyping Shared Resource
Testis (slide 1): Seminiferous tubular degeneration and atrophy, multifocal (-2 tubules), mild.
Diaphragm (slide 2): NSML.
Patient No: 8
ID #: 2162
Species: Mouse
Tests Ordered:
GEM: Yes
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart, lung and kidney (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with macrovacuolar hepatocellular lipidosis, random,
multifocal, mild.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Testis (slide 1): Seminiferous tubular degeneration and atrophy, focal (-1 tubule), mild.
Diaphragm (slide 2): NSML.
Patient No: 9
ID #: 2179
Species: Mouse
Tests Ordered:
GEM: Yes
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart, lung and kidney (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild with multifocal random areas
consistent with microvacuolar hepatocellular lipidosis.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, moderate characterized by multifocal prominent germinal centers.
Testis (slide 1): Seminiferous tubular degeneration and atrophy, multifocal (-3 tubules), mild.
Diaphragm (slide 2): NSML.
Patient No: 10
ID #: 2180
Species: Mouse
Tests Ordered:
GEM: Yes
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart (slide 1): NSML.
Lung (slide 1): There are multifocal small aggregates of lymphocytes in the peribronchiolar and perivascular interstitium.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild with multifocal, random areas
Accession # 2013-2-219
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Phenotyping Shared Resource
consistent with micro- to macrovacuolar hepatocellular lipidosis.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Testis (slide 1): Seminiferous tubular degeneration and atrophy, multifocal (-7 tubules), mild.
Kidney (slide 1): There is a focally extensive area of lymphocytes in the interstitium, and multifocal (3) small areas of
cortical tubular regeneration.
Diaphragm (slide 2): NSML.
Patient No: 11
ID #: 2205
Species: Mouse
Tests Ordered:
GEM: Yes
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart and lung (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, centrilobular to midzonal, mild with multifocal
areas consistent with micro- to macrovacuolar hepatocellular lipidosis.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Testis (slide 1): Seminiferous tubular degeneration and atrophy, multifocal (-5 tubules), mild.
Kidney (slide 1): Lumens of few (presumptive) distal tubules multifocally distributed in the cortex are mildly ectatic and
lined by low columnar epithelial cells.
Diaphragm (slide 2): NSML.
Patient No: 12
ID #: 2436
Species: Mouse
Tests Ordered:
GEM: Yes
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart and and kidney (slide 1): NSML.
Lung (slide 1): Acidophilic macrophage pneumonia, multifocal, mild with intrabronchiolar crystals and lymphocytes in the
peribronchiolar and perivascular interstitium.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Testis (slide 1): Seminiferous tubular degeneration and atrophy, multifocal (-32 tubules), moderate.
Diaphragm (slide 2): NSML.
Patient No: 13
ID #: 1964
Species: Mouse
Tests Ordered:
GEM: Yes
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Accession # 2013-2-219
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Phenotyping Shared Resource
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart, lung and kidney (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Testis (slide 1): Seminiferous tubular degeneration and atrophy, focal (-1 tubule), mild.
Diaphragm (slide 2): NSML.
Patient No: 14
ID #: 1965
Species: Mouse
Tests Ordered:
GEM: Yes
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart, lung and kidney (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Testis (slide 1): Seminiferous tubular degeneration and atrophy, focal (-1 tubule), mild.
Diaphragm (slide 2): NSML.
Patient No: 15
ID #: 2406
Species: Mouse
Tests Ordered:
GEM: No
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart, lung and testis (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Kidney (slide 1): There is a focally extensive area of lymphoplasmacytic aggregates in the interstitium.
Diaphragm (2 sections; slide 2): NSML.
Patient No: 16
ID #: 1876
Species: Mouse
Tests Ordered:
GEM: No
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex:
Accession # 2013-2-219
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Male intact
Anatomic Pathology
Microscopic Findings
Heart, spleen and kidney (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, centrilobular to midzonal, mild with multifocal
areas consistent with micro- to macrovacuolar hepatocellular lipidosis.
Testis (slide 1): Seminiferous tubular degeneration and atrophy, multifocal (-9 tubules), mild.
Lung (slide 1): There are multifocal small aggregates of lymphocytes in the peribronchiolar and perivascular interstitium.
Diaphragm (2 sections; slide 2): NSML.
Patient No: 17
ID #: 1899
Species: Mouse
Tests Ordered:
GEM: No
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart (slide 1): Aorta (presumptive), mural chrondroid metaplasia, focal, mild.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild with perivascular
lymphocytes.
Lung and testis (slide 1): NSML.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, moderate characterized by multifocal prominent germinal centers.
Kidney (slide 1): There is focal area of mild cortical tubular regeneration.
Diaphragm (2 sections; slide 2): NSML.
Patient No: 18
ID #: 1903
Species: Mouse
Tests Ordered:
GEM: No
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart (slide 1): NSML.
Lung (slide 1): Pulmonary adenoma, focal with multifocal aggregates of lymphocytes in the perivascular and
peribronchiolar interstitium.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild with multifocal areas
consistent with micro- to macrovacuolar hepatocellular lipidosis.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Testis (slide 1): Seminiferous tubular degeneration and atrophy, multifocal (-2 tubules), mild.
Kidney (slide 1): There are multifocal (2) areas of mild tubular epithelial regeneration.
Diaphragm (2 sections; slide 2): NSML.
Tests Ordered:
Accession # 2013-2-219
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Phenotyping Shared Resource
Patient No: 19
ID #: 1872
Species: Mouse
GEM: No
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart, lung, liver and testis (slide 1): NSML.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Kidney (slide 1): Lumens of (presumptive) distal tubules multifocally distributed in the cortex are moderately ectatic and
lined by low columnar epithelial cells.
Diaphragm (slide 2): NSML.
Patient No: 20
ID #: 1874
Species: Mouse
Tests Ordered:
GEM: No
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart, lung and spleen (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild with focal perivascular
lymphocytes.
Testis (slide 1): Seminiferous tubular degeneration and atrophy, multifocal (-7 tubules), mild.
Kidney (slide 1): There is a focal aggregate of interstitial lymphocytes.
Diaphragm (2 sections; slide 2): There are multifocal (2) aggregates of lymphocytes attached to the diaphragm.
Patient No: 21
ID #: 1875
Species: Mouse
Tests Ordered:
GEM: No
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart, lung, spleen and testis (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild.
Kidney (slide 1): There are multifocal aggregates of lymphocytes and plasma cells in the interstitium.
Diaphragm (2 sections; slide 2): NSML.
Patient No: 22
ID #:
Accession # 2013-2-219
GEM: No
Construct:
Tests Ordered:
Slide Evaluation
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Phenotyping Shared Resource
1870
Species: Mouse
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart, lung and testis (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with micro- to macrovacuolar hepatocellular lipidosis,
centrilobular to midzonal, mild.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Kidney (slide 1): Lumens of (presumptive) distal tubules multifocally distributed in the cortex are moderately ectatic and
lined by low columnar epithelial cells.
Diaphragm (slide 2): NSML.
Patient No: 23
ID #: 1967
Species: Mouse
Tests Ordered:
GEM: No
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart and testis (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild.
Lung (slide 1): Focally there is a single aggregate of lymphocytes in the peribronchiolar interstitium.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Kidney (slide 1): There is a focal area of both interstitial lymphocytes and cortical tubular regeneration.
Diaphragm (slide 2): NSML.
Patient No: 24
ID #: 2159
Species: Mouse
Tests Ordered:
GEM: No
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart, lung, kidney, liver and testis (slide 1): NSML.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Diaphragm (slide 2): NSML.
Patient No: 25
ID #: 2207
Accession # 2013-2-219
GEM: No
Construct:
Tests Ordered:
Slide Evaluation
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Comparative Pathology & Mouse
Phenotyping Shared Resource
Species: Mouse
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart, lung, kidney and testis (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Diaphragm (slide 2): NSML.
Patient No: 26
ID #: 2435
Species: Mouse
Tests Ordered:
GEM: No
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart and lung (slide 1): NSML.
Liver (2 sections; slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Testis (slide 1): Seminiferous tubular degeneration and atrophy, multifocal (-28 tubules), moderate.
Kidney (slide 1): There is a focal aggregate of lymphocytes and plasma cells in the interstitium, and 2 medullary tubules
dilated by hyaline, proteinaceous material.
Diaphragm (slide 2): NSML.
Patient No: 27
ID #: 2437
Species: Mouse
Tests Ordered:
GEM: No
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed: C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart, lung, spleen and kidney (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild.
Testis (slide 1): Seminiferous tubular degeneration and atrophy, multifocal (-3 tubules), mild.
Diaphragm (slide 2): NSML.
Patient No: 28
ID #: 2206
Species: Mouse
Tests Ordered:
GEM: No
Slide Evaluation
Construct:
Promoter
Gene
Genotype
Strain/Breed:
Accession # 2013-2-219
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C57BL/6
Age/DOB: 12/1/11
Sex: Male intact
Anatomic Pathology
Microscopic Findings
Heart, lung, kidney and testis (slide 1): NSML.
Liver (slide 1): Hepatocellular vacuolar change consistent with glycogen, widespread, mild.
Spleen (slide 1): Lymphoid hyperplasia, multifocal, mild characterized by multifocal prominent germinal centers.
Diaphragm (slide 2): NSML.
Comments and Interpretation
There do not appear to be any treatment-related lesions in any of the tissues evaluated histologically.
One injected wildtype mouse (1903) had a focal pulmonary adenoma. Primary pulmonary adenomas and
adenocarcinomas are some of the most common tumors noted in older mice, with incidences of up to 36% and 16%,
respectively. Wild-type GR, BALB, and A mice are particularly more prone to develop spontaneous pulmonary tumors,
while wild-type B6 mice are relatively resistant. A spectrum of hyperplasia and neoplasia has also been associated with
administration of benzopyrene. The cell of origin is either the Clara cell or type II pneumocyte.
Mice in 3/4 groups (injected MYOT: 2027, 1868, 1869, 1969; control MYOT: 2205; injected wildtype: 1872, 1870) had
variable numbers of renal cortical tubules in which the lumens were ectatic. These tubules were presumed to be distal
tubules, and appeared to be lined by viable epithelial cells with no evidence of degeneration or necrosis. These ectatic
lumens did not contain protein, casts or crystals. The cause and significance of this is not known.
Mice in each group (injected MYOT: 1868, 2161; control MYOT: 2180; injected wildtype: 1899, 1903; control wildtype:
1967) had basophilic tubules indicative of tubular regeneration and chronic progressive nephropathy which occurs in
aging mice and rats. Isolated tubules were affected in each mice and therefore were likely not clinically significant.
Most mice had evidence of hepatocellular vacuolar change in the liver, consistent with glycogenosis and/or micro- to
macrovacuolar hepatocellular lipidosis. The glycogen content of the liver varies depending on the physiological state of
the animal. Glycogen accumulation can also be observed as a manifestation of toxicity or with glycogen storage diseases.
Hepatic lipidosis, also known as steatosis, fatty change, cytoplasmic vacuolization, etc. is a common hepatic lesion in
mice. It is due to an accummulation of triglycerides, either spontaneously or as a response to toxic agents with different
lobular locations reflecting differences in metabolic activation of the hepatotoxin.
One injected MYOT mouse (2160) had centrilobular to midzonal hepatocellular hypertrophy. This hypertrophy typically
represents changes in mitochondria, smooth endoplasmic reticulum (cytochrome P450 monooxygenase activities) and/or
peroxisomes, and requires examination of liver at the ultrastructural level for definitive organelle identification. This is a
common adaptive response to a range of stimuli, including pregnancy and lactation, hormonal fluctuations, dietary
constituents, infections associated with acute phase proteins as well as responses to xenobiotic exposure. Note that
while most constitutively expressed P450s and other phase I metabolism enzymes have a predominant centrilobular
localization, this hypertrophic response is generally not considered a toxic effect.
Most mice in all groups had lymphoid hyperplasia in the spleen, characterized by multifocal prominent germinal centers
within white pulp. Due to it s presence in all groups, this lesion is considered incidental and attributed to non-specific
antigenic stimulation.
Multiple mice in all groups had a limited number of seminiferous tubules in the testis which were characterized by
degenerative spermatogenic epithelium consistent with mild atrophy. The date of death was not provided, but the date of
birth was noted to be December 2011. Therefore, it is presumed that these mice are >1 year, hence the testicular atrophy
is age-associated.
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One control MYOT mouse (2436) had acidophilic macrophage pneumonia in the lung. Eosinophilic crystal-laden alveolar
macrophages were originally diagnosed as acidophilic macrophage pneumonia (AMP) in various strains (NMRI, T x HT,
C57BL) of mice back in 1990 (Veterinary Pathology 27: 274-281, 1990). Since then, AMP has been reported in various
genetically engineered mice on C57BL/6, 129, and B6;129 backgrounds. AMP can be severe enough to produce clinical
illness and be a major cause of death in control populations (Pathology of Genetically Engineered Mice. JM Ward, JF
Mahler, RR Maronpot, JP Sundberg (eds). 1st Edition, Iowa State University Press, 2000.). Although not reported in this
mouse, hyalinosis is an associated lesion whereby epithelial cells with intensely eosinophilic cytoplasm can be found in
the nasal cavity, lung, glandular stomach, gall bladder, bile and pancreatic ducts, and ureter. These eosinophilic proteins
have been identified as chitinase 3-like 3 (Chi3l3) [formerly, Ym-1, also known as eosinophil chemotactic factor (ECF-L)]
and the highly related Ym-2 (95% identity) (Journal of Biological Chemistry 275: 8032-8037, 2000; American Journal of
Pathology 158: 323-332, 2001; Journal of Biological Chemistry 277; 5468-5475, 2002). Chi3l3/Ym-1 is a unique functional
marker for alternatively activated macrophages in Th2-mediated inflammatory responses.
Chondroid metaplasia of great vessels, such as the aorta of injected wildtype mouse 1899 is occasionally seen. Proposed
underlying cases include local hypoxia.
Microscopic aggregates of lymphocytes, as noted in the lung, kidney, liver and/or diaphragm of multiple mice, can be
found widely distributed in the lungs, mediastinum, subcutaneous fascia, intestinal tract, urinary bladder, kidneys, etc. of
mice, especially older mice. These lymphocytic aggregates are typically distributed as small perivascular cuffs, and are
not in themselves indicative of pathology.
Tissue: N/A
Blocks: N/A
Frozen Specimens: No
Slides: Returned to PI
Photographs: N/A
Resident: Not applicable
Pathologist: Krista M. D. La Perle, DVM, PhD, Dipl. ACVP
Accession # 2013-2-219
Reported: 4/11/2013
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