Analysis Tools
reproductive system
 |
• on days 9 and 16 of pregnancy, mutant glands show reduced gland size and weight and are less dense than wild-type
• mutant alveolar units are very small and display a disrupted architecture
|
|
• homozygotes show a 40% decrease in litter size at first pregnancy
• litter size continues to decline in multiparous females
|
endocrine/exocrine glands
|
|
• on pregnancy day 16 and lactation day 3, mutant glands display a decreased proliferation index, with significantly fewer Ki-67 positive cells than wild-type glands
|
|
|
• virgin and adult homozygotes display retarded mammary gland development relative to wild-type controls
• mutant glands are smaller and less dense at 3-week or 11-week old, pregnant and lactating homozygotes
|
|
|
• at 11 weeks of age, virgin mutant glands display much less elaborated alveolar structures and a 3-fold reduction in ductal tips, suggesting decreased branching morphogenesis
• however, mammary gland weight is normal at 11 weeks
|
|
|
• on lactation day 3, mutant alveolar structures resemble those seen in wild-type glands at 3 weeks postpartum, with alveolar sacs appearing to be undergoing early stages of involution
• transcriptome profiling of mutant lactating glands revealed an involution-related gene signature relative to wild-type glands
• lactating mutant glands exhibit decreased Stat5 and AKT signaling along with increased Stat3 signaling, suggesting precocious involution of the mammary gland through reduced cell survival signals
|
|
|
• on lactation days 1 and 3, mutant glands show reduced gland size and weight and are less dense than wild-type
• mutant alveolar units are very small and display a disrupted architecture
• on lactation day 3, mutant alveolar structures resemble those seen in wild-type glands at 3 weeks postpartum
|
|
|
• on days 9 and 16 of pregnancy, mutant glands show reduced gland size and weight and are less dense than wild-type
• mutant alveolar units are very small and display a disrupted architecture
|
|
|
• at 3 weeks, virgin homozygotes display a ~3-fold reduction in the number of terminal end buds (TEBs) relative to wild-type controls
|
|
|
• alveolar development is completely defective during pregnancy and lactation, with smaller and partially closed alveolar sacs
• at 3 weeks postpartum, mutant glands appear highly malformed, disorganized, and contain fewer alveolar structures
• in matrigel culture, mutant mammary epithelial cells (MECs) form smaller unorganized alveolar structures that fail to differentiate into multi-lobular structures in the presence of prolactin, unlike wild-type MECs; however, addition of recombinant IGFBP7 is sufficient to restore the alveolar differentiation defect
|
|
|
• although mutant glands are capable of producing milk during lactation days 1 and 3, they appear to have less beta-casein staining on day 3 than wild-type controls
• on lactation day 1, cytoplasmic lipid droplets are observed, unlike in wild-type glands
• however, female homozygotes are fertile and capable of nursing their pups
|
integument
|
|
• on pregnancy day 16 and lactation day 3, mutant glands display a decreased proliferation index, with significantly fewer Ki-67 positive cells than wild-type glands
|
|
|
• virgin and adult homozygotes display retarded mammary gland development relative to wild-type controls
• mutant glands are smaller and less dense at 3-week or 11-week old, pregnant and lactating homozygotes
|
|
|
• at 11 weeks of age, virgin mutant glands display much less elaborated alveolar structures and a 3-fold reduction in ductal tips, suggesting decreased branching morphogenesis
• however, mammary gland weight is normal at 11 weeks
|
|
|
• on lactation day 3, mutant alveolar structures resemble those seen in wild-type glands at 3 weeks postpartum, with alveolar sacs appearing to be undergoing early stages of involution
• transcriptome profiling of mutant lactating glands revealed an involution-related gene signature relative to wild-type glands
• lactating mutant glands exhibit decreased Stat5 and AKT signaling along with increased Stat3 signaling, suggesting precocious involution of the mammary gland through reduced cell survival signals
|
|
|
• on lactation days 1 and 3, mutant glands show reduced gland size and weight and are less dense than wild-type
• mutant alveolar units are very small and display a disrupted architecture
• on lactation day 3, mutant alveolar structures resemble those seen in wild-type glands at 3 weeks postpartum
|
|
|
• on days 9 and 16 of pregnancy, mutant glands show reduced gland size and weight and are less dense than wild-type
• mutant alveolar units are very small and display a disrupted architecture
|
|
|
• at 3 weeks, virgin homozygotes display a ~3-fold reduction in the number of terminal end buds (TEBs) relative to wild-type controls
|
|
|
• alveolar development is completely defective during pregnancy and lactation, with smaller and partially closed alveolar sacs
• at 3 weeks postpartum, mutant glands appear highly malformed, disorganized, and contain fewer alveolar structures
• in matrigel culture, mutant mammary epithelial cells (MECs) form smaller unorganized alveolar structures that fail to differentiate into multi-lobular structures in the presence of prolactin, unlike wild-type MECs; however, addition of recombinant IGFBP7 is sufficient to restore the alveolar differentiation defect
|
|
|
• although mutant glands are capable of producing milk during lactation days 1 and 3, they appear to have less beta-casein staining on day 3 than wild-type controls
• on lactation day 1, cytoplasmic lipid droplets are observed, unlike in wild-type glands
• however, female homozygotes are fertile and capable of nursing their pups
|
growth/size/body
|
• surviving mutant pups show a persistent decrease in body weight through postpartum day 12, consistent with reduced beta-casein expression in the lactating glands
|
cellular
|
• in culture, mutant mouse embryonic fibroblasts (MEFs) show decreased proliferation potential relative to wild-type MEFs
|
|
|
• on pregnancy day 16 and lactation day 3, mutant glands display a decreased proliferation index, with significantly fewer Ki-67 positive cells than wild-type glands
|
