Analysis Tools
mortality/aging
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• although homozygotes develop to maturity with no apparent abnormalities in size, weight, and agility, they exhibit a shortened lifespan of ~15 months relative to wild-type littermates which survive for >2 years
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• male homozygotes display a progressive reduction in fecundity over time and through successive generations
• male infertility is caused by a gradual accumulation of chromosomal defects, particularly aneuploidies, in male germ cells
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hematopoietic system
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• two deceased homozygotes, 8 and 10 months old, displayed an enlarged spleen, with an increase in lymphocytic cells in the white pulp
• a less severe spleen enlargement is also observed in some homozygotes at 10 months of age
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immune system
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• two deceased homozygotes, 8 and 10 months old, displayed an enlarged spleen, with an increase in lymphocytic cells in the white pulp
• a less severe spleen enlargement is also observed in some homozygotes at 10 months of age
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• a less severe enlargement of the axillary lymph nodes is observed at 10 months of age
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• two deceased homozygotes, 8 and 10 months old, displayed hypertrophy of the submandibular lymph nodes
• a less severe enlargement is also observed in some homozygotes at 10 months of age
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• aging homozygotes develop inflammatory responses of increasing severity in multiple organs
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• at 10 months of age, 1 of 4 homozygotes displayed gastritis
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• 1 of 2 deceased homozygotes displayed pancreatitis
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• two deceased homozygotes, 8 and 10 months old, displayed severe glomerulonephritis
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dermatitis
(
J:69405
)
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• at 10-12 months of age, homozygotes display an increased incidence of ulcerative dermatitis relative to wild-type littermates
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renal/urinary system
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• perivascular infiltrates are observed in the kidney of some homozygotes at 10 months of age
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• two deceased homozygotes, 8 and 10 months old, displayed severe glomerulonephritis
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reproductive system
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• male homozygotes display a progressive reduction in fecundity over time and through successive generations
• male infertility is caused by a gradual accumulation of chromosomal defects, particularly aneuploidies, in male germ cells
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• homozygotes display an increased incidence of chromosomal defects, particularly aneuploidies, resulting from improper resolution of double-Holliday junctions
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• female homozygotes exhibit a progressive reduction in fecundity over time and through successive generations
• notably, female fertility appears to be less severely compromised than male fertility
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• the litter size in crosses of homozygous mutant mice decreases over time and through successive generations
• reduction in fertility of homozygotes appears to reflect embryonic death rather than impaired fertilization
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digestive/alimentary system
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• two deceased homozygotes, 8 and 10 months old, displayed lymphocytic perivascular infiltrates in the salivary glands
• perivascular infiltrates are also observed in the salivary glands of some homozygotes at 10 months of age
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• at 10 months of age, 1 of 4 homozygotes displayed gastritis
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endocrine/exocrine glands
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• two deceased homozygotes, 8 and 10 months old, displayed lymphocytic perivascular infiltrates in the salivary glands
• perivascular infiltrates are also observed in the salivary glands of some homozygotes at 10 months of age
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• a less severe hyperplasia of the pancreatic islets is observed in some homozygotes at 10 months of age
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• 1 of 2 deceased homozygotes displayed pancreatitis
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respiratory system
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• 1 of 2 deceased homozygotes displayed lymphocytic perivascular infiltrates in the lungs
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cellular
aneuploidy
(
J:82397
)
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• infertile male homozygotes show a high incidence (~15%) of chromosomal aberrations, mostly aneuploidies, in meiotic metaphase I (MI) spermatocytes
• 19 of 225 sets of mutant MI chromosomes showed loss of one of the painted autosome or sex chromosome pairs, 10 showed a loss of either an X or Y chromosome, and 2 showed loss of more than one painted chromosome pair, while hyperploidy was observed in two sets of the chromosomes, one with an extra painted autosome pair, and the other with an extra Y chromosome; in contrast, wild-type metaphases showed a low incidence of aneuploidy among the painted chromosomes (2/188), and no other types of chromosomal anomalies
• numeric anomalies were also noted in meiotic metaphase II (MII) chromosomes in mutant, but not wild-type, testicular cells: hypoploidy was found in 10 cells and hyperploidy in 8 cells of a total of 129 sets of MII chromosomes
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integument
dermatitis
(
J:69405
)
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• at 10-12 months of age, homozygotes display an increased incidence of ulcerative dermatitis relative to wild-type littermates
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growth/size/body
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• two deceased homozygotes, 8 and 10 months old, displayed an enlarged spleen, with an increase in lymphocytic cells in the white pulp
• a less severe spleen enlargement is also observed in some homozygotes at 10 months of age
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