behavior/neurological phenotype

• abnormal sexual interaction
  • 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
  (MGI Ref ID J:66582)

• abnormal spatial learning
  • Normal - however, ovariectomized mice treated with 17beta-estradiol exhibit normal escape from a cued water maze
  (MGI Ref ID J:75472)
  • ovariectomized mice treated with 17beta-estradiol exhibit reduced escape platform learning in a Morris water maze compared with similarly treated wild-type mice
  (MGI Ref ID J:75472)
  • ovariectomized mice exhibit slower escape time from a Morris water maze compared with similarly treated wild-type mice
  (MGI Ref ID J:75472)

• increased aggression towards males
  • 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
  (MGI Ref ID J:66582)
  • younger mice and naive (not used in sexual behavior assays) mice display increased aggression compared to wild-type controls
  (MGI Ref ID J:66582)

renal/urinary system phenotype

• abnormal urinary bladder urothelium morphology
  • at >3 months of age, male homozygotes exhibit epithelial hyperplasia in the bladder wall
  (MGI Ref ID J:51663)

cardiovascular system phenotype

• increased systemic arterial blood pressure
  • increased blood pressure in most mice at 6-7 months of age
  (MGI Ref ID J:73898)
  • blood pressure remains elevated to 22 months of age
  (MGI Ref ID J:73898)
  • heart rate unchanged
  (MGI Ref ID J:73898)

• abnormal vascular smooth muscle morphology
  • vascular smooth muscle cells are half normal size
  (MGI Ref ID J:73898)

• abnormal vascular smooth muscle physiology
  • absence of voltage dependent outward current
  (MGI Ref ID J:73898)

• increased vasoconstriction
  (MGI Ref ID J:73898)

reproductive system phenotype

• decreased ovulation rate
  • cles fail to fully respond and discharge their oocytes in response to hCG
  (MGI Ref ID J:51663)
  • 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
  (MGI Ref ID J:51663)
  • 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
  (MGI Ref ID J:51663)

• reduced female fertility
  • 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)
  (MGI Ref ID J:51663)
  • Normal - in contrast, young, sexually mature male homozygotes reproduce normally
  (MGI Ref ID J:51663)

• impaired ovarian folliculogenesis
  • 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
  (MGI Ref ID J:51663)

• abnormal cumulus oophorus morphology
  • 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
  (MGI Ref ID J:51663)

• prostate gland epithelial hyperplasia
  • at >3 months of age, male homozygotes exhibit epithelial hyperplasia in the prostatic collecting ducts
  (MGI Ref ID J:51663)

• decreased corpora lutea number
  • upon superovulation, ovaries from immature (25-31 days) female homozygotes display fewer corpora lutea than ovaries from stimulated wild-type females
  (MGI Ref ID J:51663)
  • at 7-9 weeks of age, young adult female homozygotes display ovaries with less corpora lutea relative to wild-type mice
  (MGI Ref ID J:51663)

• anovulation
  • upon superovulation, 2 of 11 immature (25-31 days) female homozygotes yield no detectable ova
  (MGI Ref ID J:51663)

• decreased litter size
  • 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)
  (MGI Ref ID J:51663)

respiratory system phenotype

• abnormal lung morphology
  • lungs contain leukocyte, mainly granulocytes with some B lymphocytes, macrophages and eosinophils, infiltration unlike in wild-type mice
  (MGI Ref ID J:83617)

skeleton phenotype

• increased compact bone area
  • load-induced increase in cortical area is reduced 2-fold compared to in similarly treated wild-type mice
  (MGI Ref ID J:91765)

• myelofibrosis
  • at 2 years, mice develop myelofibrosis unlike wild-type mice
  (MGI Ref ID J:83617)

• increased osteoblast cell number
  • after 10 minutes of mechanical stress, the number of osteoblast-like cells is increased more than in similarly treated wild-type mice
  (MGI Ref ID J:91765)

• abnormal bone mineralization
  • load-induced increase in periosteal mineralization is decreased 50% compared to in similarly treated wild-type mice
  (MGI Ref ID J:91765)

cellular phenotype

• abnormal cumulus oophorus morphology
  • 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
  (MGI Ref ID J:51663)

• increased keratinocyte apoptosis
  • in hair matrix keratinocytes
  (MGI Ref ID J:107589)

endocrine/exocrine gland phenotype

• impaired ovarian folliculogenesis
  • 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
  (MGI Ref ID J:51663)

• decreased corpora lutea number
  • at 7-9 weeks of age, young adult female homozygotes display ovaries with less corpora lutea relative to wild-type mice
  (MGI Ref ID J:51663)
  • upon superovulation, ovaries from immature (25-31 days) female homozygotes display fewer corpora lutea than ovaries from stimulated wild-type females
  (MGI Ref ID J:51663)

• prostate gland epithelial hyperplasia
  • at >3 months of age, male homozygotes exhibit epithelial hyperplasia in the prostatic collecting ducts
  (MGI Ref ID J:51663)

• abnormal cumulus oophorus morphology
  • 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
  (MGI Ref ID J:51663)

growth/size/body region phenotype

• enlarged liver
  • with leukocyte, mainly granulocytes with some B lymphocytes, infiltration
  (MGI Ref ID J:83617)

• enlarged spleen
  • profound by 1.5 years of age with leukocyte infiltration
  (MGI Ref ID J:83617)

• spleen hyperplasia
  (MGI Ref ID J:83617)

hearing/vestibular/ear phenotype

• abnormal cochlear IHC afferent innervation pattern
  • 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
  (MGI Ref ID J:108892)
  • Normal - 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
  (MGI Ref ID J:108892)

hematopoietic system phenotype

• abnormal B cell number
  • 17beta-estradiol-treated castrated mice exhibit a reduced decrease in the frequency of B cells compared with similarly treated wild-type mice
  (MGI Ref ID J:82423)
  • 17beta-estradiol-treated castrated mice fail to exhibit a decrease in newly formed B cells unlike similarly treated wild-type mice
  (MGI Ref ID J:82423)
  • Normal - however, 17beta-estradiol-treated castrated mice exhibit decreases in pre-B and pro-B cells
  (MGI Ref ID J:82423)

• increased granulocyte number
  • granulocyte populations in the bone marrow are increased 15% to 30% compared to in wild-type mice
  (MGI Ref ID J:83617)
  • absolute numbers of granulocytes are increased 2-fold compared to in wild-type mice
  (MGI Ref ID J:83617)

• increased neutrophil cell number
  • in the blood at 1.5 years of age
  (MGI Ref ID J:83617)

• spleen hypoplasia
  • 17beta-estradiol-treated ovariectomized mice exhibit a reduction in spleen cellularity unlike similarly treated wild-type mice
  (MGI Ref ID J:110416)

• abnormal leukopoiesis
  • granulopoiesis is enhanced compared to in wild-type mice
  (MGI Ref ID J:83617)

• enlarged spleen
  • profound by 1.5 years of age with leukocyte infiltration
  (MGI Ref ID J:83617)

• increased monocyte cell number
  • in the blood at 1.5 years of age
  (MGI Ref ID J:83617)

• abnormal bone marrow cell number
  • 17beta-estradiol-treated castrated mice fail to exhibit a decrease in bone marrow cellularity unlike similarly treated wild-type mice
  (MGI Ref ID J:82423)

• anemia
  • at 2 years in surviving mice
  (MGI Ref ID J:83617)

• increased bone marrow cell number
  • as early as 1 month of age
  (MGI Ref ID J:83617)

• increased megakaryocyte cell number
  • in the spleen and bone marrow
  (MGI Ref ID J:83617)

• increased pre-B cell number
  (MGI Ref ID J:83617)

• increased pro-B cell number
  (MGI Ref ID J:83617)

• abnormal lymphopoiesis
  • at 1.5 years, some mice exhibit lymphoid blast crisis unlike in wild-type mice
  (MGI Ref ID J:83617)

• increased erythrocyte cell number
  • at 2 years, mice exhibit accumulation of red blood cells unlike in wild-type mice
  (MGI Ref ID J:83617)

• increased leukocyte cell number
  • at 1.5 years, leukocyte numbers in the blood is increased 3- to 4-fold compared to in wild-type mice
  (MGI Ref ID J:83617)

• spleen hyperplasia
  (MGI Ref ID J:83617)

homeostasis/metabolism phenotype

• increased circulating insulin-like growth factor I level
  • 17beta-estradiol-treated ovariectomized mice fail to exhibit a reduction in IGF-1 serum levels unlike similarly treated wild-type mice
  (MGI Ref ID J:110416)

• abnormal response/metabolism to endogenous compounds
  • Normal - however, 17beta-estradiol-treated ovariectomized mice exhibit normal reduction in thymus weight and cellularity
  (MGI Ref ID J:110416)
  • 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
  (MGI Ref ID J:82423)
  • Normal - however, 17beta-estradiol-treated castrated mice exhibit immunoglobulin switching and increased immunoglobulin levels
  (MGI Ref ID 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
  (MGI Ref ID J:110416)
  • 17beta-estradiol-treated ovariectomized mice exhibit a reduction in spleen cellularity unlike similarly treated wild-type mice
  (MGI Ref ID J:110416)

immune system phenotype

• abnormal B cell number
  • 17beta-estradiol-treated castrated mice fail to exhibit a decrease in newly formed B cells unlike similarly treated wild-type mice
  (MGI Ref ID J:82423)
  • 17beta-estradiol-treated castrated mice exhibit a reduced decrease in the frequency of B cells compared with similarly treated wild-type mice
  (MGI Ref ID J:82423)
  • Normal - however, 17beta-estradiol-treated castrated mice exhibit decreases in pre-B and pro-B cells
  (MGI Ref ID J:82423)

• enlarged spleen
  • profound by 1.5 years of age with leukocyte infiltration
  (MGI Ref ID J:83617)

• abnormal leukopoiesis
  • granulopoiesis is enhanced compared to in wild-type mice
  (MGI Ref ID J:83617)

• abnormal lymphopoiesis
  • at 1.5 years, some mice exhibit lymphoid blast crisis unlike in wild-type mice
  (MGI Ref ID J:83617)

• enlarged lymph nodes
  • by 1.5 years of age
  (MGI Ref ID J:83617)

• increased monocyte cell number
  • in the blood at 1.5 years of age
  (MGI Ref ID J:83617)

• spleen hypoplasia
  • 17beta-estradiol-treated ovariectomized mice exhibit a reduction in spleen cellularity unlike similarly treated wild-type mice
  (MGI Ref ID J:110416)

• increased pro-B cell number
  (MGI Ref ID J:83617)

• increased leukocyte cell number
  • at 1.5 years, leukocyte numbers in the blood is increased 3- to 4-fold compared to in wild-type mice
  (MGI Ref ID J:83617)

• increased pre-B cell number
  (MGI Ref ID J:83617)

• increased neutrophil cell number
  • in the blood at 1.5 years of age
  (MGI Ref ID J:83617)

• spleen hyperplasia
  (MGI Ref ID J:83617)

• increased granulocyte number
  • absolute numbers of granulocytes are increased 2-fold compared to in wild-type mice
  (MGI Ref ID J:83617)
  • granulocyte populations in the bone marrow are increased 15% to 30% compared to in wild-type mice
  (MGI Ref ID J:83617)

integument phenotype

• increased keratinocyte apoptosis
  • in hair matrix keratinocytes
  (MGI Ref ID J:107589)

• accelerated hair follicle regression
  • apoptosis of hair follicle and hair matrix keratinocyte is increased compared to in wild-type mice confirming accelerated apoptosis-driven hair follicle regression
  (MGI Ref ID J:107589)

• thin epidermis
  • dermal thickness is less than in wild-type mice
  (MGI Ref ID J:107589)

• abnormal hair cycle catagen phase
  • at P17 and P19, more hair follicles are in catagen than in wild-type mice
  (MGI Ref ID J:107589)

liver/biliary system phenotype

• enlarged liver
  • with leukocyte, mainly granulocytes with some B lymphocytes, infiltration
  (MGI Ref ID J:83617)

mammalian phenotype

• skeleton phenotype
  • Normal - unlike in Esr1 null mice, no defects are detected in the skeletal system
  (MGI Ref ID J:62222)

• behavior/neurological phenotype
  • Normal - unlike mice null for Esr1, no defect in retention is detected in an inhibitory avoidance behavior assay
  (MGI Ref ID J:65785)

• reproductive system phenotype
  • Normal - 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
  (MGI Ref ID J:51663)

muscle phenotype

• abnormal vascular smooth muscle morphology
  • vascular smooth muscle cells are half normal size
  (MGI Ref ID J:73898)

• abnormal muscle electrophysiology
  • absence of voltage dependent outward current in vascular smooth muscle cells
  (MGI Ref ID J:73898)

• increased vasoconstriction
  (MGI Ref ID J:73898)

• abnormal vascular smooth muscle physiology
  • absence of voltage dependent outward current
  (MGI Ref ID J:73898)

neoplasm

• increased chronic myelocytic leukemia incidence
  • mice exhibit a myeloproliferative disease with granulocytosis and massive blast cell infiltration of hematopoietic and nonhematopoietic organs
  (MGI Ref ID J:83617)

nervous system phenotype

• abnormal astrocyte morphology
  • at 2 months of age, male homozygotes display hypertrophic astroglial cells, with swollen cell bodies and thicker processes relative to wild-type mice
  (MGI Ref ID J:67862)
  • t 2 years of age
  (MGI Ref ID J:67862)
  • 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
  (MGI Ref ID J:67862)
  • 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
  (MGI Ref ID J:67862)

• abnormal substantia nigra morphology
  • by 2 yrs of age, homozygotes exhibit severe degeneration of neuronal cell bodies in the substantia nigra
  (MGI Ref ID J:67862)

• decreased brain size
  • Normal - however, no differences in overall brain size are observed at 2 months or at 1 year of age
  (MGI Ref ID J:67862)
  • at 2 years of age, mutant brains are significantly smaller than wild-type, exhibiting obvious atrophy in the somatosensory-parietal cortex
  (MGI Ref ID J:67862)

• abnormal cochlear IHC afferent innervation pattern
  • 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
  (MGI Ref ID J:108892)
  • Normal - 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
  (MGI Ref ID J:108892)

• decreased neuron number
  • 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
  (MGI Ref ID J:67862)
  • 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
  (MGI Ref ID J:67862)
  • at 2 months of age, neuronal loss is much more pronounced in male than in female homozygotes
  (MGI Ref ID J:67862)
  • Normal - 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
  (MGI Ref ID J:67862)
  • 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
  (MGI Ref ID J:67862)
  • rsal raphe nucleus, locus coeruleus, solitary tract nucleus, medial preoptic area, and medial amygdala nucleus
  (MGI Ref ID J:67862)

• abnormal somatosensory cortex morphology
  • 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
  (MGI Ref ID J:67862)
  • 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
  (MGI Ref ID J:67862)

• astrocytosis
  • only a mild increase of GFAP immunoreactivity is detected in the hippocampus and cerebellum
  (MGI Ref ID J:67862)
  • 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
  (MGI Ref ID J:67862)
  • Normal - strikingly, no astrogliosis is observed in regions of the somatosensory cortex with severe neuronal loss
  (MGI Ref ID J:67862)

• neuron degeneration
  • Normal - however, no shrinkage of neuronal cell bodies is noted in mutant brains at 2 months of age
  (MGI Ref ID J:67862)
  • at 2 yrs of age, homozygotes exhibit degeneration of neuronal cell bodies throughout the brain, esp. in the substantia nigra
  (MGI Ref ID J:67862)
  • Normal - no neurofibrillary tangles or Lewy bodies are ever observed, even at 2 yrs of age
  (MGI Ref ID J:67862)

• abnormal neocortex morphology
  • 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
  (MGI Ref ID J:67862)

cellular phenotype

• abnormal enterocyte apoptosis
  • a few apoptotic cells are found in the colonic epithelium compared to in wild-type mice
  (MGI Ref ID J:107308)

• abnormal enterocyte proliferation
  • colonic cells exhibit a 1.6-fold higher than in wild-type mice
  (MGI Ref ID J:107308)

digestive/alimentary phenotype

• abnormal large intestine crypts of Lieberkuhn morphology
  • Normal - however, mice exhibit normal crypt length, crypt area, nuclear density, number of cells per crypt, and occurrence of aberrant crypt foci
  (MGI Ref ID J:107308)
  • in the distal colon, mucin appears as large globs in the upper crypts and on top of the crypts unlike in wild-type mice
  (MGI Ref ID J:107308)

• colitis
  • Normal - however, lymphoid infiltration at 12 months is less severe
  (MGI Ref ID J:107308)
  • at 4 months, mice exhibit lymphoid infiltration below the epithelium in the colon unlike wild-type mice
  (MGI Ref ID J:107308)

• abnormal enterocyte proliferation
  • colonic cells exhibit a 1.6-fold higher than in wild-type mice
  (MGI Ref ID J:107308)

• abnormal enterocyte morphology
  • colonic epithelial cells exhibit reduced expression of differentiation markers compared to in wild-type mice
  (MGI Ref ID J:107308)
  • colonic epithelium cells exhibit abnormal tight junctions and desmosomes compared to in wild-type mice
  (MGI Ref ID J:107308)

• abnormal enterocyte apoptosis
  • a few apoptotic cells are found in the colonic epithelium compared to in wild-type mice
  (MGI Ref ID J:107308)

• abnormal enterocyte physiology
  • colonic cells exhibit increased migration to the luminal surface compared with wild-type mice
  (MGI Ref ID J:107308)

behavior/neurological phenotype

• impaired cued conditioning behavior
  • in male mice
  (MGI Ref ID J:115451)

• impaired contextual conditioning behavior
  • during fear conditioning, mice exhibit an impairment in memory for context compared with wild-type mice
  (MGI Ref ID J:115451)

• abnormal behavior
  • when suspended by their tails, fasted mice exhibit tremulousness, disturbed gait and balance, and spinning movement unlike similarly treated wild-type mice
  (MGI Ref ID J:151012)

endocrine/exocrine gland phenotype

• enlarged pancreatic islets
  • mice exhibit a reduction in the percent of small islets and an increase in the percent of larger islets compared to in wild-type mice
  (MGI Ref ID J:151012)
  • the average islet area is larger than in wild-type mice
  (MGI Ref ID J:151012)

• decreased insulin secretion
  • following glucose stimulation, peak insulin secretion is delayed compared to in similarly treated wild-type mice
  (MGI Ref ID J:151012)

• abnormal large intestine crypts of Lieberkuhn morphology
  • in the distal colon, mucin appears as large globs in the upper crypts and on top of the crypts unlike in wild-type mice
  (MGI Ref ID J:107308)
  • Normal - however, mice exhibit normal crypt length, crypt area, nuclear density, number of cells per crypt, and occurrence of aberrant crypt foci
  (MGI Ref ID J:107308)

• abnormal mammary gland growth during lactation
  • on day 6 of lactation, lobuloalveolar development only partially penetrates the fat pad and the alveoli are enlarged unlike in wild-type mice
  (MGI Ref ID J:125583)

• abnormal mammary gland epithelium morphology
  • at day 6 of lactation, mammary gland exhibits increased visible adipose tissue and reduced epithelium compared to in wild-type mice
  (MGI Ref ID J:125583)

• abnormal mammary gland growth during pregnancy
  • mid-pregnancy lobuloalveolar development is not as extensive as in wild-type mice
  (MGI Ref ID J:125583)

• mammary gland alveolar hyperplasia
  • on day 6 of lactation
  (MGI Ref ID J:125583)

growth/size/body region phenotype

• cardiac hypertrophy
  • after 8 months, mice exhibit ventricular hypertrophy compared with wild-type mice
  (MGI Ref ID J:93438)

• enlarged heart
  • after 8 months
  (MGI Ref ID J:93438)

• increased body length
  • at 4, but not 18, months
  (MGI Ref ID J:111108)

• increased heart weight
  • in sham-operated mice
  (MGI Ref ID J:108991)

• increased body weight
  • following induced myocardial infarction
  (MGI Ref ID J:108991)

hearing/vestibular/ear phenotype

• abnormal auditory brainstem response
  • following accoustic trauma, mice exhibit a greater shift in brainstem auditory evoked potential compared with similarly treated wild-type mice
  (MGI Ref ID J:135833)

homeostasis/metabolism phenotype

• abnormal response/metabolism to endogenous compounds
  • 17beta-estradiol-induced relaxation of aortic rings is more pronounced than in similarly treated wild-type rings
  (MGI Ref ID J:64165)

• decreased circulating glucose level
  • in fasting mice prior to and after tamoxifen treatment
  (MGI Ref ID J:151012)

• increased urine glycosaminoglycan level
  • Normal - however, male mice have normal urine glycosaminoglycan content
  (MGI Ref ID J:122274)
  • female mice exhibit an increase in urinary glycosaminoglycan content compared with wild-type mice
  (MGI Ref ID J:122274)

• abnormal response to cardiac infarction
  • Normal - however, infarct size is normal
  (MGI Ref ID J:108991)
  • following induced myocardial infarction, mice exhibit increased body weight and mortality, pleural effusions, and ascites compared with similarly treated wild-type mice
  (MGI Ref ID J:108991)

• decreased insulin secretion
  • following glucose stimulation, peak insulin secretion is delayed compared to in similarly treated wild-type mice
  (MGI Ref ID J:151012)

• ascites
  • following induced myocardial infarction
  (MGI Ref ID J:108991)

• increased circulating glucose level
  • in fed mice
  (MGI Ref ID J:151012)

• increased insulin sensitivity
  (MGI Ref ID J:151012)

cardiovascular system phenotype

• abnormal myocardial fiber morphology
  • after 8 months, the distance between myocytes is increased compared to in wild-type mice
  (MGI Ref ID J:93438)
  • myofibrils exhibit irregular orientation and heterogeneous length unlike in wild-type mice
  (MGI Ref ID J:93438)
  • cardiomyocytes contain abnormal nuclear envelops
  (MGI Ref ID J:93438)

• abnormal intercalated disk morphology
  • intercalating disks are more convoluted than in wild-type hearts with greater membrane lengths
  (MGI Ref ID J:93438)

• abnormal response to cardiac infarction
  • Normal - however, infarct size is normal
  (MGI Ref ID J:108991)
  • following induced myocardial infarction, mice exhibit increased body weight and mortality, pleural effusions, and ascites compared with similarly treated wild-type mice
  (MGI Ref ID J:108991)

• dilated heart ventricle
  • after 8 months
  (MGI Ref ID J:93438)

• increased vasodilation
  • 17beta-estradiol-induced relaxation of aortic rings is more pronounced than in similarly treated wild-type rings
  (MGI Ref ID J:64165)

• enlarged heart
  • after 8 months
  (MGI Ref ID J:93438)

• cardiac hypertrophy
  • after 8 months, mice exhibit ventricular hypertrophy compared with wild-type mice
  (MGI Ref ID J:93438)

• enlarged myocardial fiber
  • after 8 months, the diameter of myocytes is increased compared to in wild-type mice
  (MGI Ref ID J:93438)

• increased heart weight
  • in sham-operated mice
  (MGI Ref ID J:108991)

immune system phenotype

• colitis
  • at 4 months, mice exhibit lymphoid infiltration below the epithelium in the colon unlike wild-type mice
  (MGI Ref ID J:107308)
  • Normal - however, lymphoid infiltration at 12 months is less severe
  (MGI Ref ID J:107308)

• urinary bladder inflammation
  • female mice exhibit an increase in T cell and macrophage infiltration in the female bladders unlike in wild-type mice
  (MGI Ref ID J:122274)

integument phenotype

• abnormal mammary gland epithelium morphology
  • at day 6 of lactation, mammary gland exhibits increased visible adipose tissue and reduced epithelium compared to in wild-type mice
  (MGI Ref ID J:125583)

• abnormal mammary gland growth during lactation
  • on day 6 of lactation, lobuloalveolar development only partially penetrates the fat pad and the alveoli are enlarged unlike in wild-type mice
  (MGI Ref ID J:125583)

• mammary gland alveolar hyperplasia
  • on day 6 of lactation
  (MGI Ref ID J:125583)

• abnormal mammary gland growth during pregnancy
  • mid-pregnancy lobuloalveolar development is not as extensive as in wild-type mice
  (MGI Ref ID J:125583)

limbs/digits/tail phenotype

• long femur
  • at 2 and 4, but not 18, months
  (MGI Ref ID J:111108)

mortality/aging

• increased sensitivity to induced morbidity/mortality
  • following induced myocardial infarction
  (MGI Ref ID J:108991)

muscle phenotype

• abnormal intercalated disk morphology
  • intercalating disks are more convoluted than in wild-type hearts with greater membrane lengths
  (MGI Ref ID J:93438)

• abnormal myocardial fiber morphology
  • cardiomyocytes contain abnormal nuclear envelops
  (MGI Ref ID J:93438)
  • after 8 months, the distance between myocytes is increased compared to in wild-type mice
  (MGI Ref ID J:93438)
  • myofibrils exhibit irregular orientation and heterogeneous length unlike in wild-type mice
  (MGI Ref ID J:93438)

• increased vasodilation
  • 17beta-estradiol-induced relaxation of aortic rings is more pronounced than in similarly treated wild-type rings
  (MGI Ref ID J:64165)

• enlarged myocardial fiber
  • after 8 months, the diameter of myocytes is increased compared to in wild-type mice
  (MGI Ref ID J:93438)

• abnormal muscle contractility
  • during fatiguing stimulation, male mice exhibit less of a decrease in force compared with similarly treated wild-type mice
  (MGI Ref ID J:95398)
  • during recovery from fatiguing stimulation, male mice exhibit higher force generation than similarly treated wild-type mice
  (MGI Ref ID J:95398)

nervous system phenotype

• abnormal excitatory postsynaptic potential
  • female mice exhibit poorer fast synaptic transmission compared with wild-type mice
  (MGI Ref ID J:115451)

• reduced long term potentiation
  • in female mice
  (MGI Ref ID J:115451)

renal/urinary system phenotype

• abnormal urinary bladder physiology
  • bladder permeability in female mice is higher than in wild-type mice
  (MGI Ref ID J:122274)

• increased urine glycosaminoglycan level
  • Normal - however, male mice have normal urine glycosaminoglycan content
  (MGI Ref ID J:122274)
  • female mice exhibit an increase in urinary glycosaminoglycan content compared with wild-type mice
  (MGI Ref ID J:122274)

• abnormal urinary bladder urothelium morphology
  • female mice exhibit ulceration and atrophy of bladder urothelium unlike in wild-type mice
  (MGI Ref ID J:122274)

• abnormal urinary bladder morphology
  • Normal - however, bladders of male mice are normal
  (MGI Ref ID J:122274)
  • at 8 months, female mice exhibit epithelial atrophy, massive ulceration of the bladder, and invasion of immune cells into the stroma and epithelium unlike in wild-type mice
  (MGI Ref ID J:122274)

• urinary bladder inflammation
  • female mice exhibit an increase in T cell and macrophage infiltration in the female bladders unlike in wild-type mice
  (MGI Ref ID J:122274)

reproductive system phenotype

• abnormal mammary gland growth during pregnancy
  • mid-pregnancy lobuloalveolar development is not as extensive as in wild-type mice
  (MGI Ref ID J:125583)

respiratory system phenotype

• abnormal pulmonary alveolus morphology
  • female mice exhibit an accumulation of surfactant inside the alveolar spaces unlike in wild-type mice
  (MGI Ref ID J:89974)
  • Normal - however, lung alveoli morphology is normal at P14 and 4 weeks
  (MGI Ref ID J:89974)
  • female, but not male, 3 month old mice exhibit larger and fewer alveoli compared with wild-type mice
  (MGI Ref ID J:89974)

• abnormal surfactant physiology
  • female mice exhibit an accumulation of surfactant inside the alveolar spaces unlike in wild-type mice
  (MGI Ref ID J:89974)

skeleton phenotype

• abnormal long bone epiphyseal plate morphology
  • the number of proliferative chondrocytes per column is increased while the number of hypertrophic chondrocytes per column is decreased compared to in wild-type mice
  (MGI Ref ID J:111108)

• long femur
  • at 2 and 4, but not 18, months
  (MGI Ref ID J:111108)

cardiovascular system phenotype

• abnormal response of heart to induced stress
  • female mice treated with isoproterenol prior to ischemia, exhibit less recovery of postischemic function compared with similarly treated wild-type mice
  (MGI Ref ID J:101968)

homeostasis/metabolism phenotype

• decreased physiological sensitivity to xenobiotic
  • female mice treated with isoproterenol prior to ischemia, exhibit less recovery of postischemic function, phosphocreatine, and ATP compared with similarly treated wild-type mice
  (MGI Ref ID J:101968)

• increased circulating luteinizing hormone level
  • higher than normal luteinizing hormone levels are further elevated by ovariectomy
  (MGI Ref ID J:118736)

• abnormal response of heart to induced stress
  • female mice treated with isoproterenol prior to ischemia, exhibit less recovery of postischemic function compared with similarly treated wild-type mice
  (MGI Ref ID J:101968)

behavior/neurological phenotype

• abnormal nociception after inflammation
  • female mice exhibit an increased threshold to mechanical nociception following inflammation compared with similarly treated wild-type female mice
  (MGI Ref ID J:151022)
  • Normal - however, male mice exhibit normal mechanical nociception after inflammation
  (MGI Ref ID J:151022)

• decreased exploration in new environment
  • in an elevated plus maze, mice spend less time exploring the open arms compared with wild-type mice
  (MGI Ref ID J:101943)

• increased anxiety-related response
  • in an elevated plus maze, mice spend less time exploring the open arms compared with wild-type mice
  (MGI Ref ID J:101943)

• hyporesponsive to tactile stimuli
  • Normal - however, male mice exhibit normal mechanical nociception
  (MGI Ref ID J:151022)
  • female mice exhibit an increased threshold to mechanical nociception compared with similarly treated wild-type female mice
  (MGI Ref ID J:151022)

homeostasis/metabolism phenotype

• decreased serotonin level
  • serotonin levels are decreased in the stria terminalis, preoptic area, and hippocampus compared to in wild-type mice
  (MGI Ref ID J:101943)

• decreased dopamine level
  • in the caudate putamen
  (MGI Ref ID J:101943)

nervous system phenotype

• decreased serotonin level
  • serotonin levels are decreased in the stria terminalis, preoptic area, and hippocampus compared to in wild-type mice
  (MGI Ref ID J:101943)