Analysis Tools
reproductive system
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• at 8.5 days post-partum, lobuloalveolar development is impaired with smaller and more compacted lobuloalveoli, indicating reduced secretory activation or slowed milk secretion into the alveolar luminal space
• however, females are able to support pup weight gain post-partum and no difference in estrogen or progesterone receptor expression is seen in mammary epithelial cells
• transplantation of homozygous Tnfaip3m1Apb mammary epithelial tissue into wild-type hosts rescues mammary branching morphogenesis during pregnancy
• transplantation of homozygous Tnfaip3m1Apb ovaries into wild-type hosts results in fully developed mammary glands 12 days after pregnancy
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• a non-significant trend towards a reduced number of corpus luteum bodies is observed
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• number of secondary follicles is significantly lower than in wild-type females
• however, ovarian area and primary follicle numbers are normal
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• uteri show sub-clinical inflammation with thickening of the uterine wall and presence of an immune infiltrate along the uterine wall but no overt signs of tissue damage
• digested uteri show an increased frequency of macrophages (CD45+ CD11b+ F4/80+ cells) and of ICAM-1+ macrophages, consistent with an increased inflammatory state
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• for those females that successfully get pregnant, average time to pregnancy is 39 days versus 23 days for wild-type females
• however, the average number of viable pups per litter is normal
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• at 5-8 weeks of age, females spend significantly more days in diestrous, or completely fail to enter estrous
• cervical swabs contain a significantly higher number of neutrophils at all estrous cycle stages than in wild-type females, indicating failure to reach true estrous or exit diestrous
• transplantation of homozygous Tnfaip3m1Apb ovaries into ovariectomized wild-type recipients rescues the estrous cycle
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short estrus
(
J:324062
)
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• when paired with wild-type males for 100 days, 30% of adult (8- to 12-wk-old) females fail to get pregnant
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endocrine/exocrine glands
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• adult 14-week old virgin females show impaired mammary gland development
• at 10 weeks of age, developing mammary glands show increased protein levels of osteoprotegerin (OPG) and RANKL paracrine hormones, along with reduced NIK stabilization and decreased levels of P100 to P52 processing, indicating decreased non-canonical NF-kappaB signaling
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• ductal morphogenesis is partially rescued by pregnancy
• adult 14-week old virgin females show a marked reduction in ductal elongation in the 3rd (axial) and 4th (inguinal) mammary glands along with grossly enlarged lymph nodes
• transplantation of homozygous Tnfaip3m1Apb mammary epithelial tissue into wild-type hosts rescues post-pubertal mammary ductal elongation
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• at 8.5 days post-partum, lobuloalveolar development is impaired with smaller and more compacted lobuloalveoli, indicating reduced secretory activation or slowed milk secretion into the alveolar luminal space
• however, females are able to support pup weight gain post-partum and no difference in estrogen or progesterone receptor expression is seen in mammary epithelial cells
• transplantation of homozygous Tnfaip3m1Apb mammary epithelial tissue into wild-type hosts rescues mammary branching morphogenesis during pregnancy
• transplantation of homozygous Tnfaip3m1Apb ovaries into wild-type hosts results in fully developed mammary glands 12 days after pregnancy
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• at 8.5 days post-partum, the mammary epithelium completely penetrates the mammary fat pad but lobuloalveolar development is impaired, as shown by smaller and more compacted lobuloalveoli relative to wild-type females
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• a non-significant trend towards a reduced number of corpus luteum bodies is observed
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• number of secondary follicles is significantly lower than in wild-type females
• however, ovarian area and primary follicle numbers are normal
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homeostasis/metabolism
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• following a 16-hour fast, 16-wk-old females exhibit lower blood glucose levels than wild-type controls
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• females show a ~50% reduction in serum LH levels relative to wild-type controls, along with a decrease in Lhb (luteinizing hormone beta) mRNA and a trend towards increased levels of Gnrh1 (gonadotropin releasing hormone 1) mRNA in hypothalamic-pituitary lysates
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• following i.v. injection of glucose (1 g/kg), females show significantly higher blood insulin levels than wild-type controls, with a greater effect observed at 32 weeks than at 52 weeks of age
• homozygous Tnfaip3m1Apb recipients harboring wild-type islets show 3 times higher blood insulin levels than wild-type islets transplanted into wild-type recipients, suggesting systemic inflammation, extrinsic to the pancreatic beta cell
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• during proestrus, serum progesterone levels are significantly higher than in wild type-females
• however, serum estradiol levels during bona fide proestrus and diestrus are normal
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• females release up to 3 times more insulin in the blood than wild-type controls in response to a glucose bolus and exhibit features of peripheral insulin resistance
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• at 10 weeks of age, mammary glands show increased protein levels of RANKL relative to wild-type glands
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• at 10 weeks of age, mammary glands show increased protein levels of osteoprotegerin (OPG) relative to wild-type glands
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immune system
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• females exhibit an increased frequency of CD44+ T cells in the spleen, lymph nodes and peripheral blood relative to wild-type controls
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• females exhibit an increased frequency of ICAM1+ splenic macrophages relative to wild-type controls
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• females show a significantly smaller microglial diameter, an increased number of Iba-1+ microglia with an activated morphometry and a more ramified phenotype in the hypothalamus than wild-type controls
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• adult 14-week old virgin females show grossly enlarged lymph nodes in the 3rd (axial) and 4th (inguinal) mammary glands
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• females exhibit spontaneous CNS inflammation, associated with low levels of luteinizing hormone
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• uteri show sub-clinical inflammation with thickening of the uterine wall and presence of an immune infiltrate along the uterine wall but no overt signs of tissue damage
• digested uteri show an increased frequency of macrophages (CD45+ CD11b+ F4/80+ cells) and of ICAM-1+ macrophages, consistent with an increased inflammatory state
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nervous system
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• females show a significantly smaller microglial diameter, an increased number of Iba-1+ microglia with an activated morphometry and a more ramified phenotype in the hypothalamus than wild-type controls
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• females exhibit spontaneous CNS inflammation, associated with low levels of luteinizing hormone
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hematopoietic system
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• females exhibit an increased frequency of CD44+ T cells in the spleen, lymph nodes and peripheral blood relative to wild-type controls
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• females exhibit an increased frequency of ICAM1+ splenic macrophages relative to wild-type controls
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• females show a significantly smaller microglial diameter, an increased number of Iba-1+ microglia with an activated morphometry and a more ramified phenotype in the hypothalamus than wild-type controls
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integument
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• adult 14-week old virgin females show impaired mammary gland development
• at 10 weeks of age, developing mammary glands show increased protein levels of osteoprotegerin (OPG) and RANKL paracrine hormones, along with reduced NIK stabilization and decreased levels of P100 to P52 processing, indicating decreased non-canonical NF-kappaB signaling
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• ductal morphogenesis is partially rescued by pregnancy
• adult 14-week old virgin females show a marked reduction in ductal elongation in the 3rd (axial) and 4th (inguinal) mammary glands along with grossly enlarged lymph nodes
• transplantation of homozygous Tnfaip3m1Apb mammary epithelial tissue into wild-type hosts rescues post-pubertal mammary ductal elongation
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• at 8.5 days post-partum, lobuloalveolar development is impaired with smaller and more compacted lobuloalveoli, indicating reduced secretory activation or slowed milk secretion into the alveolar luminal space
• however, females are able to support pup weight gain post-partum and no difference in estrogen or progesterone receptor expression is seen in mammary epithelial cells
• transplantation of homozygous Tnfaip3m1Apb mammary epithelial tissue into wild-type hosts rescues mammary branching morphogenesis during pregnancy
• transplantation of homozygous Tnfaip3m1Apb ovaries into wild-type hosts results in fully developed mammary glands 12 days after pregnancy
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• at 8.5 days post-partum, the mammary epithelium completely penetrates the mammary fat pad but lobuloalveolar development is impaired, as shown by smaller and more compacted lobuloalveoli relative to wild-type females
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