Analysis Tools
reproductive system
| N |
• at 7-9 weeks of age, female homozygotes display normal mammary gland histology and appear to lactate efficiently, as judged by normal nursing behavior and growth of their pups
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• at >3 months of age, male homozygotes exhibit epithelial hyperplasia in the prostatic collecting ducts
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• at 7-9 weeks of age, young adult female homozygotes display ovaries with less corpora lutea relative to wild-type mice
• upon superovulation, ovaries from immature (25-31 days) female homozygotes display fewer corpora lutea than ovaries from stimulated wild-type females
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• upon superovulation, immature (25-31 days) female homozygotes display a reduction in the cellular mass of the oocyte cumulus relative to wild-type and heterozygous littermates
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• more early atretic follicles at 7-9 weeks of age
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• at 7-9 weeks of age, young adult female homozygotes display ovaries with more early atretic follicles and fewer corpora lutea relative to wild-type mice, suggesting partial arrest of follicular development and less frequent follicular maturation
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• ovaries from superovulated immature female homozygotes display a large number of mature oocytes, indicating a normal response to pregnant mare serum gonadotropin, but contain less corpora lutea than stimulated wild-type ovaries, suggesting that some follicles fail to fully respond and discharge their oocytes in response to hCG
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• upon superovulation, immature (25-31 days) female homozygotes display an average yield of 6.0 +/- 1.5 oocytes per female, whereas wild-type and heterozygous females yield 33.7 +/- 4.8 and 52.5 +/- 5.7 oocytes per female, respectively
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• upon superovulation, 2 of 11 immature (25-31 days) female homozygotes yield no detectable ova
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• female homozygotes show normal sexual behavior but produce significantly fewer litters than wild-type females (1.7 +/- 1.0 vs 2.8 +/- 0.4 litters/female, respectively)
• in contrast, young, sexually mature male homozygotes reproduce normally
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• female homozygotes show a significantly reduced litter size relative to wild-type females (3.1 +/- 1.8 vs 8.8 +/- 2.5 pups/litter, respectively)
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growth/size/body
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• with leukocyte, mainly granulocytes with some B lymphocytes, infiltration
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• profound by 1.5 years of age with leukocyte infiltration
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nervous system
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• at 2 months of age, male homozygotes display hypertrophic astroglial cells, with swollen cell bodies and thicker processes relative to wild-type mice
• at 2 months of age, an increase in the number of hypertrophic astrocytes is also observed in the white matter adjacent to regions of neuronal loss
• at 1 year of age, both male and female homozygotes show a mild to moderate increase in the number of astrocytes relative to wild-type counterparts; however, no significant differences in the number or morphology of GFAP immunoreactive cells are observed at 2 years of age
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astrocytosis
(
J:67862
)
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• at 2 months of age, male homozygotes show an increased number of GFAP-immunoreactive cells throughout many brain areas, esp. in the basal forebrain, hypothalamus, and amygdala; females are less affected than males
• only a mild increase of GFAP immunoreactivity is detected in the hippocampus and cerebellum
• strikingly, no astrogliosis is observed in regions of the somatosensory cortex with severe neuronal loss
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• at 2-6 months of age, female homozygotes exhibit some dilated afferent nerve endings on the cochlear IHCs, in the absence of a swollen stria vascularis
• however, middle and inner ear morphology is relatively normal relative to heterozygotes, and positive estrogen receptor alpha immunostaining is noted at the same locations as in control CBA/Ca mice
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• at 2 years of age, mutant brains are significantly smaller than wild-type, exhibiting obvious atrophy in the somatosensory-parietal cortex
• however, no differences in overall brain size are observed at 2 months or at 1 year of age
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• by 2 yrs of age, homozygotes exhibit severe degeneration of neuronal cell bodies in the substantia nigra
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• at 2 months of age, homozygotes display hypocellularity of the neocortex, with severe neuronal deficit in layers II, III, IV and V, extending from the somatosensory region to the parietal region
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• at 2 months of age, homozygotes display a significant reduction in the number of neurons in layer II, III, IV, and V of the somatosensory cortex
• by 2 years of age, an obvious atrophy affecting all layers is noted in the somatosensory-parietal cortex; however, thinning of layers IV and V is particularly pronounced
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• at 2 months of age, homozygotes display a severe neuronal deficit in layers II, III, IV and V of the neocortex, as well as significant neuronal loss in the basal forebrain, hypothalamus, amygdala, ventral tegmental area, substantia nigra, central gray, dorsal raphe nucleus, locus coeruleus, solitary tract nucleus, medial preoptic area, and medial amygdala nucleus
• at 2 months of age, neuronal loss is much more pronounced in male than in female homozygotes
• at 1 year of age, both male and female homozygotes exhibit neuronal hypocellularity in the same brain regions, but the overall brain size is still similar to that of wild-type counterparts
• at 2 years of age, homozygotes show a decreased number of small neurons in layers II, III, IV, and V of the somatosensory cortex, as well as loss of large pyramidal neurons in layer V
• no obvious neuronal deficit is found in the paraventricular nucleus of hypothalamus (PVN), hippocampus, caudate-putamen, thalamus, or cerebellum at 2 months of age or later
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• at 2 yrs of age, homozygotes exhibit degeneration of neuronal cell bodies throughout the brain, esp. in the substantia nigra
• however, no shrinkage of neuronal cell bodies is noted in mutant brains at 2 months of age
• no neurofibrillary tangles or Lewy bodies are ever observed, even at 2 yrs of age
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immune system
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• profound by 1.5 years of age with leukocyte infiltration
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• granulopoiesis is enhanced compared to in wild-type mice
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• at 1.5 years, some mice exhibit lymphoid blast crisis unlike in wild-type mice
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• 17beta-estradiol-treated castrated mice exhibit a reduced decrease in the frequency of B cells compared with similarly treated wild-type mice
• 17beta-estradiol-treated castrated mice fail to exhibit a decrease in newly formed B cells unlike similarly treated wild-type mice
• however, 17beta-estradiol-treated castrated mice exhibit decreases in pre-B and pro-B cells
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• at 1.5 years, leukocyte numbers in the blood is increased 3- to 4-fold compared to in wild-type mice
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• granulocyte populations in the bone marrow are increased 15% to 30% compared to in wild-type mice
• absolute numbers of granulocytes are increased 2-fold compared to in wild-type mice
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• in the blood at 1.5 years of age
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• in the blood at 1.5 years of age
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• 17beta-estradiol-treated ovariectomized mice exhibit a reduction in spleen cellularity unlike similarly treated wild-type mice
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• by 1.5 years of age
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cardiovascular system
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• vascular smooth muscle cells are half normal size
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• increased blood pressure in most mice at 6-7 months of age
• blood pressure remains elevated to 22 months of age
• heart rate unchanged
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• absence of voltage dependent outward current
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skeleton
| N |
• unlike in Esr1 null mice, no defects are detected in the skeletal system
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myelofibrosis
(
J:83617
)
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• at 2 years, mice develop myelofibrosis unlike wild-type mice
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• load-induced increase in cortical area is reduced 2-fold compared to in similarly treated wild-type mice
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• after 10 minutes of mechanical stress, the number of osteoblast-like cells is increased more than in similarly treated wild-type mice
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• load-induced increase in periosteal mineralization is decreased 50% compared to in similarly treated wild-type mice
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endocrine/exocrine glands
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• at >3 months of age, male homozygotes exhibit epithelial hyperplasia in the prostatic collecting ducts
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• at 7-9 weeks of age, young adult female homozygotes display ovaries with less corpora lutea relative to wild-type mice
• upon superovulation, ovaries from immature (25-31 days) female homozygotes display fewer corpora lutea than ovaries from stimulated wild-type females
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• upon superovulation, immature (25-31 days) female homozygotes display a reduction in the cellular mass of the oocyte cumulus relative to wild-type and heterozygous littermates
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• more early atretic follicles at 7-9 weeks of age
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• at 7-9 weeks of age, young adult female homozygotes display ovaries with more early atretic follicles and fewer corpora lutea relative to wild-type mice, suggesting partial arrest of follicular development and less frequent follicular maturation
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hearing/vestibular/ear
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• at 2-6 months of age, female homozygotes exhibit some dilated afferent nerve endings on the cochlear IHCs, in the absence of a swollen stria vascularis
• however, middle and inner ear morphology is relatively normal relative to heterozygotes, and positive estrogen receptor alpha immunostaining is noted at the same locations as in control CBA/Ca mice
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renal/urinary system
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• at >3 months of age, male homozygotes exhibit epithelial hyperplasia in the bladder wall
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muscle
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• vascular smooth muscle cells are half normal size
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• absence of voltage dependent outward current
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• absence of voltage dependent outward current in vascular smooth muscle cells
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hematopoietic system
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• profound by 1.5 years of age with leukocyte infiltration
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• granulopoiesis is enhanced compared to in wild-type mice
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• at 1.5 years, some mice exhibit lymphoid blast crisis unlike in wild-type mice
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• 17beta-estradiol-treated castrated mice fail to exhibit a decrease in bone marrow cellularity unlike similarly treated wild-type mice
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• as early as 1 month of age
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• in the spleen and bone marrow
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• at 2 years, mice exhibit accumulation of red blood cells unlike in wild-type mice
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• 17beta-estradiol-treated castrated mice exhibit a reduced decrease in the frequency of B cells compared with similarly treated wild-type mice
• 17beta-estradiol-treated castrated mice fail to exhibit a decrease in newly formed B cells unlike similarly treated wild-type mice
• however, 17beta-estradiol-treated castrated mice exhibit decreases in pre-B and pro-B cells
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• at 1.5 years, leukocyte numbers in the blood is increased 3- to 4-fold compared to in wild-type mice
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• granulocyte populations in the bone marrow are increased 15% to 30% compared to in wild-type mice
• absolute numbers of granulocytes are increased 2-fold compared to in wild-type mice
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• in the blood at 1.5 years of age
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• in the blood at 1.5 years of age
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• 17beta-estradiol-treated ovariectomized mice exhibit a reduction in spleen cellularity unlike similarly treated wild-type mice
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homeostasis/metabolism
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• 17beta-estradiol-treated ovariectomized mice fail to exhibit a reduction in IGF-1 serum levels unlike similarly treated wild-type mice
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• 17beta-estradiol-treated castrated mice fail to exhibit a decrease in bone marrow cellularity and exhibit a reduced decrease in the frequency of B cells unlike similarly treated wild-type mice
(J:82423)
• however, 17beta-estradiol-treated castrated mice exhibit immunoglobulin switching and increased immunoglobulin levels
(J:82423)
• 17beta-estradiol-treated ovariectomized mice fail to exhibit a reduction in the cortex area ration of the thymus, alterations in thymocyte frequencies, or reduced IGF-1 serum levels unlike similarly treated wild-type mice
(J:110416)
• 17beta-estradiol-treated ovariectomized mice exhibit a reduction in spleen cellularity unlike similarly treated wild-type mice
(J:110416)
• however, 17beta-estradiol-treated ovariectomized mice exhibit normal reduction in thymus weight and cellularity
(J:110416)
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behavior/neurological
| N |
• unlike mice null for Esr1, no defect in retention is detected in an inhibitory avoidance behavior assay
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• ovariectomized mice exhibit slower escape time from a Morris water maze compared with similarly treated wild-type mice
• ovariectomized mice treated with 17beta-estradiol exhibit reduced escape platform learning in a Morris water maze compared with similarly treated wild-type mice
• however, ovariectomized mice treated with 17beta-estradiol exhibit normal escape from a cued water maze
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• in a resident intruder assay aggressive behaviors toward the intruder male are increased in the first trial but not in subsequent trials compared to wild-type controls
• younger mice and naive (not used in sexual behavior assays) mice display increased aggression compared to wild-type controls
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• in a 90 min test with a receptive female the number of mounts is decreased; however, the ratio of mounts and intromissions to ejaculations is reduced indicating increased sexual excitement
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• in a 90 min test with a receptive female the number of mounts is decreased
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liver/biliary system
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• with leukocyte, mainly granulocytes with some B lymphocytes, infiltration
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respiratory system
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• lungs contain leukocyte, mainly granulocytes with some B lymphocytes, macrophages and eosinophils, infiltration unlike in wild-type mice
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neoplasm
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• mice exhibit a myeloproliferative disease with granulocytosis and massive blast cell infiltration of hematopoietic and nonhematopoietic organs
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integument
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• in hair matrix keratinocytes
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• at P17 and P19, more hair follicles are in catagen than in wild-type mice
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• apoptosis of hair follicle and hair matrix keratinocyte is increased compared to in wild-type mice confirming accelerated apoptosis-driven hair follicle regression
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• dermal thickness is less than in wild-type mice
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cellular
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• at 2 months of age, male homozygotes display hypertrophic astroglial cells, with swollen cell bodies and thicker processes relative to wild-type mice
• at 2 months of age, an increase in the number of hypertrophic astrocytes is also observed in the white matter adjacent to regions of neuronal loss
• at 1 year of age, both male and female homozygotes show a mild to moderate increase in the number of astrocytes relative to wild-type counterparts; however, no significant differences in the number or morphology of GFAP immunoreactive cells are observed at 2 years of age
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astrocytosis
(
J:67862
)
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• at 2 months of age, male homozygotes show an increased number of GFAP-immunoreactive cells throughout many brain areas, esp. in the basal forebrain, hypothalamus, and amygdala; females are less affected than males
• only a mild increase of GFAP immunoreactivity is detected in the hippocampus and cerebellum
• strikingly, no astrogliosis is observed in regions of the somatosensory cortex with severe neuronal loss
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• in hair matrix keratinocytes
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