behavior/neurological
• at 10-18 weeks of age, male homozygotes exhibit significantly prolonged latencies to first mount and reduced mount frequency in response to receptive stimulus females during a 30-min sexual behavior test
• 5 of 12 male homozygotes never mounted during the observation period
• however, all mutant males sniffed and licked the genital area of stimulus females, indicating potential sexual motivation
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• 2 of 12 male homozygotes showed significant aggressive behavior (chasing and biting) towards estrous females during male copulatory tests, not observed in wild-type males
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reproductive system
• at 10-12 weeks of age, mutant ovaries lack corpora lutea
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• at 10-12 weeks of age, mutant uteri appear significantly underdeveloped relative to wild-type
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• at 10-12 weeks of age, mutant uteri weigh less than 30% of wild-type uteri
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• female homozygotes are infertile due to a disrupted ovarian cycle
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• at 14-17 weeks of age, only 1 of 10 male homozygotes gave a high mount frequency (17 times/30 min) and sired litters
• however, no differences were noted between mutant and wild-type testes weights at 12-16 weeks of age, and mutant males had active sperm in testes and epididymides
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endocrine/exocrine glands
• more salivary gland cells exhibit a fatty change than in controls
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• severe inflammatory lesions with lymphocyte infiltration and tissue destruction in the salivary glands are seen in 12 month old mice
• many CD4+ T cells and B220+ cells infiltrate the salivary glands
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• at 10-12 weeks of age, mutant ovaries lack corpora lutea
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• severe inflammatory lesions with lymphocyte infiltration and tissue destruction in the lacrimal glands are seen in 12 month old mice
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adipose tissue
• volume of abdominal white adipose tissue in females at 12 months of age is greater than in wild-type mice
• weight of white adipose tissue is increased
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• at 10-12 weeks of age, homozygotes show significantly increased internal fat relative to wild-type controls
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• proportion of dendritic cells and macrophages in the white adipose tissue is higher than in wild-type mice
• accumulated macrophages in adipose tissue forms a crown-like structure
• mice show an increase in number of F4/80+ macrophages in the cervical white adipose tissue around the salivary glands
• accumulation of mononuclear cells around adipocytes
• marker analysis suggests enhanced migration and maturation of activated M1 macrophages in the white adipose tissue
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digestive/alimentary system
• more salivary gland cells exhibit a fatty change than in controls
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• severe inflammatory lesions with lymphocyte infiltration and tissue destruction in the salivary glands are seen in 12 month old mice
• many CD4+ T cells and B220+ cells infiltrate the salivary glands
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hematopoietic system
• absolute numbers of dendritic cells in 12 month old mutants is higher
• proportion of dendritic cells in the white adipose tissue is higher than in wild-type mice
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• absolute numbers of macrophages in 12 month old mutants is higher
• proportion of macrophages in the white adipose tissue is higher than in wild-type mice
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immune system
• severe inflammatory lesions with lymphocyte infiltration and tissue destruction in the salivary glands are seen in 12 month old mice
• many CD4+ T cells and B220+ cells infiltrate the salivary glands
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• severe inflammatory lesions with lymphocyte infiltration and tissue destruction in the lacrimal glands are seen in 12 month old mice
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• absolute numbers of dendritic cells in 12 month old mutants is higher
• proportion of dendritic cells in the white adipose tissue is higher than in wild-type mice
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• absolute numbers of macrophages in 12 month old mutants is higher
• proportion of macrophages in the white adipose tissue is higher than in wild-type mice
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• mice show the development on inflammatory lesions in the lacrimal and salivary glands after 12 months of age, resembling those of human Sjogren Syndrome
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• mice exhibit higher levels of serum autoantibodies, such as anti-SSA, anti-SSB, and anti-ssDNA
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vision/eye
• severe inflammatory lesions with lymphocyte infiltration and tissue destruction in the lacrimal glands are seen in 12 month old mice
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
Sjogren's syndrome | DOID:12894 |
OMIM:270150 |
J:216958 |