Analysis Tools
endocrine/exocrine glands
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• all virgin female homozygotes exhibit abnormal mammary ductal development
• following simulation of pregnancy by E+P treatment, homozygotes exhibit varying degrees of impairment of lobuloalveolar development, with large areas of ductal epithelium lacking secondary/tertiary side branches or alveoli; a small % of homozygotes show complete absence of alveolar development
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• at maturity (8-12 weeks), all virgin female homozygotes contain mammary glands with reduced secondary and tertiary ductal branching
• following simulation of pregnancy by estrogen/progesterone (E+P) treatment, homozygotes display limited ductal secondary/tertiary side branching relative to similarly treated female heterozygotes
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• at maturity (8-12 weeks), all virgin female homozygotes exhibit significantly enlarged, cystic ducts with bloated terminal end buds; no morphological differences are noted at 5 weeks
• ductal enlargement is NOT due to accumulation of proteinaceous material in the ducts or hyperplasia of ductal luminal cells
• transplantation of mutant mammary epithelium into cleared mammary fat pads of nude mice results in primarily bloated ducts, localizing the ductal defect to the mammary epithelium
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• when cultured on Matrigel, primary mammary epithelial cells from E+P-treated homozygotes fail to functionally differentiate in response to lactogenic hormones: WAP expression is undetectable while expression of beta-casein is inhibited by 85%-100%
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reproductive system
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• female homozygotes are sterile
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homeostasis/metabolism
hypoglycemia
(
J:49673
)
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• unlike hepatectomized wild-type mice, homozygotes fail to exhibit normalization of serum glucose levels at 36-40 hrs and sustain their hypoglycemic state until 48 hrs posthepatectomy
• in contrast, serum cholesterol and triglyceride levels show no significant differences posthepatectomy
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• after partial hepatectomy, homozygotes show abnormal expression of a subset of genes involved in hepatocyte gluconeogenesis
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liver/biliary system
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• following two-thirds hepatectomy, homozygotes display impaired liver regeneration, with hepatocyte DNA synthesis reduced to 25-30% of wild-type levels at 40 hrs after surgery
• no significant differences in the rate of liver mass reconstitution are observed, suggesting that increased cellular size may be independent of DNA synthesis
• decreased liver regeneration is associated with prolonged hypoglycemia at 36-40 hrs posthepatectomy and dysregulation of several genes involved in hepatocyte gluconeogenesis and growth regulation
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integument
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• all virgin female homozygotes exhibit abnormal mammary ductal development
• following simulation of pregnancy by E+P treatment, homozygotes exhibit varying degrees of impairment of lobuloalveolar development, with large areas of ductal epithelium lacking secondary/tertiary side branches or alveoli; a small % of homozygotes show complete absence of alveolar development
|
|
|
• at maturity (8-12 weeks), all virgin female homozygotes contain mammary glands with reduced secondary and tertiary ductal branching
• following simulation of pregnancy by estrogen/progesterone (E+P) treatment, homozygotes display limited ductal secondary/tertiary side branching relative to similarly treated female heterozygotes
|
|
|
• at maturity (8-12 weeks), all virgin female homozygotes exhibit significantly enlarged, cystic ducts with bloated terminal end buds; no morphological differences are noted at 5 weeks
• ductal enlargement is NOT due to accumulation of proteinaceous material in the ducts or hyperplasia of ductal luminal cells
• transplantation of mutant mammary epithelium into cleared mammary fat pads of nude mice results in primarily bloated ducts, localizing the ductal defect to the mammary epithelium
|
|
|
• when cultured on Matrigel, primary mammary epithelial cells from E+P-treated homozygotes fail to functionally differentiate in response to lactogenic hormones: WAP expression is undetectable while expression of beta-casein is inhibited by 85%-100%
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