Analysis Tools
pigmentation
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• at 3 weeks of age, both male and female homozygotes exhibit a dull coat
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adipose tissue
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• males and females exhibited a 50% and 50% to 80% increase in gonadal fat pad weight, respectively
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• females exhibited a 50% to 80% increase in mammary fat pad weight
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endocrine/exocrine glands
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• by 21-23 weeks of age
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• marked apoptosis in granulosa cells of larger, antral size follicles at 10-12 weeks of age
• by 1 yr of age, granulosa cell apoptosis is widespread throughout the ovary, as indicated by TUNEL analysis
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• massive leukocytic infiltration with destruction of acinar cells in the salivary glands of mice fed a phytoestrogen-free diet
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• enlarged salivary glands in mice fed a phytoestrogen-free diet, although it is unclear if salivary gland/body weight ratio is normal or increased
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• massive leukocytic infiltration with destruction of acinar cells in the salivary glands of mice fed a phytoestrogen-free diet
• mice raised on a phytoestrogen-free diet develop Sjogren-like syndrome by 12-17 months of age, showing presence of massive infiltration of B220+ B lymphocytes, presence of an alpha-fodrin fragment (120 kDa) in the salivary gland, and higher levels of serum anti-fodrin antibody than wild-type mice fed this diet
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• anterior prostate weights are increased by 40%, 21%, and 25% at 8-14, 16-26, and 48-56 weeks, respectively, relative to wild-type controls
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• in the anterior lobes, hyperplasia is observed at 16-26 weeks in the absence of increased infolding of the glandular epithelium
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• dorsolateral prostate weights are increased by 54%, 55%, and 46% at 8-14, 16-26, and 48-56 weeks of age, respectively, relative to wild-type controls
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• in the dorsolateral lobes, hyperplasia is observed at 16-26 weeks in the absence of increased infolding of the glandular epithelium
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• wet weights of ventral prostates are increased by 60%, 46%, and 57% at 8-14, 16-26, and 48-56 weeks of age, respectively, relative to wild-type controls
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• at 16-26 weeks of age, male mutants display significant enlargement of the ventral, anterior and dorsolateral prostatic lobes
• increase in absolute volume of individual tissue compartments is attributed to increased volume of the entire prostate organ
• no increase in the diameter of individual ducts or localized dysplastic growth are observed in one individual cell type or tissue compartment
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• increase in combined prostate/urinary bladder weight
(J:48086)
• wet weights of the ventral, anterior and dorsolateral prostate lobes are increased at 8-14 weeks of age and maintained up to 56 weeks of age
(J:70204)
• diet (regular vs soy-free) had no significant effect on the weight or volume of prostate from animals of the same genotype
(J:70204)
• no significant differences in body weights are noted between age-matched mutant and wild-type males at all ages examined
(J:70204)
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• male mutants exhibit a hyperplasia of the entire prostate gland, which is induced at 8-14 weeks and maintained up to 56 weeks of age
• observed changes are unaffected by maintaining mice on regular or soy-free diets
• no signs of aberrant growth or enhanced malignancy are observed even at 56 weeks of age
• short-term exposure to DES resulted in comparable regression of the prostate lobes and induction of squamous metaplasia in the anterior prostate of both wild-type and mutant males
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• in the ventral prostatic lobe, hyperplasia characterized by increased infolding of the prostatic epithelium is first noted at 8-14 weeks and becomes prominent at 48-56 weeks, in the absence of epithelial dysplasia
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• increased weight of seminal vescicles, putatively due to an increased volume of secretions rather than due to structural changes
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(J:48086)
• at 10-12 weeks of age, the mutant ovary displays follicles of all types (primordial, primary secondary, and antral), but no corpora lutea
(J:63458)
• at 10-12 weeks, aberrant and non-uniform layers of granulosa cells and numerous pyknotic nuclei are detected, with marked apoptosis in granulosa cells of larger, antral size follicles
(J:63458)
• at 21-23 weeks of age, follicles at all stages are still observed but many follicles are atretic; preantral follicles are randomly scattered and many antral follicles appear cystic and hemorrhagic
(J:63458)
• by 1 yr of age, no secondary or antral follicles are identified; remnants of large follicles, many of which are cystic and hemorrhagic, are present while primary follicles consist of oddly shaped and mostly pyknotic granulosa cells
(J:63458)
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(J:48086)
• at 10-12 and 21-23 weeks and 1 yr of age
(J:63458)
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• though ovaries contained numerous follicles with abundant granulosa cells, antrum formation was arrested before ovulation
(J:48086)
• no corpora leutea
(J:48086)
(J:63458)
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• hemorrhagic cystic follicles are observed by 21-23 weeks of age
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• at 4.5 months of age, 4 of 5 male homozygotes showed normal testicular morphology, but one animal displayed grossly dysmorphic seminiferous tubules and disrupted spermatogenesis
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• at 1 yr of age, male homozygotes show a significant decrease in the volume of seminiferous epithelium
• however, no dilated lumens or other changes in the seminiferous tubule luminal volume are observed
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• at 1 yr of age, all male homozygotes show evidence of Leydig cell hyperplasia/hypertrophy, as evidenced by an increase in the absolute volume of Leydig cells per testis
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• by 1 yr of age, all male homozygotes show a reduction in testis weight
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• at 16 weeks of age, tissue levels of 5alpha-dihydrotestosterone are significantly increased in the anterior prostate of mutant males relative to wild-type males
• in contrast, tissue testosterone levels in the anterior prostate remain unchanged
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homeostasis/metabolism
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• at 16 weeks of age, serum 5alpha-dihydrotestosterone levels in mutant males are 2-fold higher than those in wild-type males
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• female testosterone level was increased to ~10 times the level in wild-type females
(J:48086)
• male testosterone levels varied though they were in general increased relative to those of control males
(J:48086)
• at 4.5 months and 1 yr of age, male serum testosterone levels are variable, with no significant increase or decrease, although levels are initially elevated at 12-14 weeks of age
(J:56358)
• at 16 weeks of age, serum testosterone levels in mutant males are ~10-fold higher than those in wild-type males
(J:70204)
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• female FSH levels were elevated 3- to 4-fold relative to wild-type females
(J:48086)
• at 4.5 months and 1 yr of age, male serum FSH levels are unchanged relative to age-matched wild-type males
(J:56358)
• female serum FSH levels are significantly higher than wild-type and heterozygous levels at 10-12 and 21-23 weeks and 1 yr of age
(J:63458)
• at 1 yr of age, female serum FSH levels are 3-fold higher than wild-type levels
(J:63458)
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• female LH levels were elevated 2- to 10-fold relative to wild-type females
(J:48086)
• LH levels were also increased in male mice
(J:48086)
• at 4.5 months and 1 yr of age, male homozygotes show elevated serum LH levels, similar to those initially reported at 12-14 weeks of age
(J:56358)
• by 1 yr of age, serum LH levels of homozygous mutant mice are ~3-fold higher than wild-type and heterozygous levels
(J:63458)
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• at 16 weeks of age, serum prolactin levels in mutant males are 3-fold higher than those in wild-type males
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• at 10-14 weeks of age, 11beta-hydroxysteroid dehydrogenase type 2 (11betaHSD2) enzyme levels remain unchanged in most tissues of female homozygotes, except in the kidney, where they are reduced to only 10% of wild-type levels
• estradiol administered to mutant females restores renal 11betaHSD2 to wild-type levels, but does not further increase levels in wild-type mice
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• in mice fed a phytoestrogen-free diet
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reproductive system
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• at 1 yr of age, no significant decreases are observed in Sertoli cell numbers or in spermatogonia and spermatocyte populations; however, significantly less round and elongated spermatids are present in the mutant epithelium relative to wild-type controls
• at 4.5 months of age, the numbers of Sertoli cells, spermatogonia, spermatocytes, round spermatids, and elongated spermatids are comparable to those of wild-type males
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(J:48086)
• at 10-12 weeks of age, the mutant ovary displays follicles of all types (primordial, primary secondary, and antral), but no corpora lutea
(J:63458)
• at 10-12 weeks, aberrant and non-uniform layers of granulosa cells and numerous pyknotic nuclei are detected, with marked apoptosis in granulosa cells of larger, antral size follicles
(J:63458)
• at 21-23 weeks of age, follicles at all stages are still observed but many follicles are atretic; preantral follicles are randomly scattered and many antral follicles appear cystic and hemorrhagic
(J:63458)
• by 1 yr of age, no secondary or antral follicles are identified; remnants of large follicles, many of which are cystic and hemorrhagic, are present while primary follicles consist of oddly shaped and mostly pyknotic granulosa cells
(J:63458)
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(J:48086)
• at 10-12 and 21-23 weeks and 1 yr of age
(J:63458)
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• though ovaries contained numerous follicles with abundant granulosa cells, antrum formation was arrested before ovulation
(J:48086)
• no corpora leutea
(J:48086)
(J:63458)
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• hemorrhagic cystic follicles are observed by 21-23 weeks of age
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• 3-fold enlargement of the clitoral gland relative to that of wild-type
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• labial folds do not develop
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• unlike in wild-type mice, mean uterine weights fail to increase significantly with age in mutant mice
• by 1 yr of age, uterine weights of homozygous mutants are only 30% of wild-type and heterozygous weights
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• underdeveloped uterus observed at 12 to 14 weeks of age
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• male homozygotes develop spermatogenic disruptions between 4.5 months and 1 yr of age, despite no significant reductions in gonadotrophins or androgens
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• at 1 yr of age, male homozygotes show a significant reduction in round and elongated spermatids, but no changes in Sertoli cells and earlier germ cells relative to wild-type males
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• male homozygotes show a specific defect in the development of spermatids during spermiogenesis
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• at 1 yr of age, tubules with early spermiogenic arrest exhibit defects in early acrosomal development
• multiple acrosomal vesicles are observed and, in some cases, acrosomes fail to uniformly spread over the spermatid nuclei
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• at 1 yr of age, the site of spermatogenic disruption appears to be early spermiogenesis with symplasts and degenerating round spermatids frequently observed
• most mutants also display some tubules with normal morphology adjacent to tubules with spermiogenic arrest, suggesting a heterogeneous disruption
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• anterior prostate weights are increased by 40%, 21%, and 25% at 8-14, 16-26, and 48-56 weeks, respectively, relative to wild-type controls
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• in the anterior lobes, hyperplasia is observed at 16-26 weeks in the absence of increased infolding of the glandular epithelium
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• dorsolateral prostate weights are increased by 54%, 55%, and 46% at 8-14, 16-26, and 48-56 weeks of age, respectively, relative to wild-type controls
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• in the dorsolateral lobes, hyperplasia is observed at 16-26 weeks in the absence of increased infolding of the glandular epithelium
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• wet weights of ventral prostates are increased by 60%, 46%, and 57% at 8-14, 16-26, and 48-56 weeks of age, respectively, relative to wild-type controls
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• at 16-26 weeks of age, male mutants display significant enlargement of the ventral, anterior and dorsolateral prostatic lobes
• increase in absolute volume of individual tissue compartments is attributed to increased volume of the entire prostate organ
• no increase in the diameter of individual ducts or localized dysplastic growth are observed in one individual cell type or tissue compartment
|
|
|
• increase in combined prostate/urinary bladder weight
(J:48086)
• wet weights of the ventral, anterior and dorsolateral prostate lobes are increased at 8-14 weeks of age and maintained up to 56 weeks of age
(J:70204)
• diet (regular vs soy-free) had no significant effect on the weight or volume of prostate from animals of the same genotype
(J:70204)
• no significant differences in body weights are noted between age-matched mutant and wild-type males at all ages examined
(J:70204)
|
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• male mutants exhibit a hyperplasia of the entire prostate gland, which is induced at 8-14 weeks and maintained up to 56 weeks of age
• observed changes are unaffected by maintaining mice on regular or soy-free diets
• no signs of aberrant growth or enhanced malignancy are observed even at 56 weeks of age
• short-term exposure to DES resulted in comparable regression of the prostate lobes and induction of squamous metaplasia in the anterior prostate of both wild-type and mutant males
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• in the ventral prostatic lobe, hyperplasia characterized by increased infolding of the prostatic epithelium is first noted at 8-14 weeks and becomes prominent at 48-56 weeks, in the absence of epithelial dysplasia
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• increased weight of seminal vescicles, putatively due to an increased volume of secretions rather than due to structural changes
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• at 4.5 months of age, 4 of 5 male homozygotes showed normal testicular morphology, but one animal displayed grossly dysmorphic seminiferous tubules and disrupted spermatogenesis
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• at 1 yr of age, male homozygotes show a significant decrease in the volume of seminiferous epithelium
• however, no dilated lumens or other changes in the seminiferous tubule luminal volume are observed
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• at 1 yr of age, all male homozygotes show evidence of Leydig cell hyperplasia/hypertrophy, as evidenced by an increase in the absolute volume of Leydig cells per testis
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• by 1 yr of age, all male homozygotes show a reduction in testis weight
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• at 1 yr of age, mutant epididymes show reduced or complete absence of sperm
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• by 21-23 weeks of age
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• at 1 yr of age, decline in round spermatid number is due to increased cell death in the adluminal compartment of the seminiferous epithelium
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• marked apoptosis in granulosa cells of larger, antral size follicles at 10-12 weeks of age
• by 1 yr of age, granulosa cell apoptosis is widespread throughout the ovary, as indicated by TUNEL analysis
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• at 16 weeks of age, tissue levels of 5alpha-dihydrotestosterone are significantly increased in the anterior prostate of mutant males relative to wild-type males
• in contrast, tissue testosterone levels in the anterior prostate remain unchanged
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anovulation
(
J:63458
)
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• female homozygotes fail to ovulate
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(J:48086)
(J:63458)
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• male homozygotes are initially fertile with normal testis morphology at 12-14 weeks, but develop progressive infertility between 4.5 months and 1 yr of age
• mutant males mated at 7 months of age for an average of 6 months fail to sire litters
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cardiovascular system
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• by 21-23 weeks of age
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• at 6 months of age, the maximum rate of change in blood pressure (dP/dT) occuring during systole is 40% higher in conscious female homozygotes relative to wild-type controls (1427 9 vs 1019 14 mm Hg/sec, respectively)
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• at 6 months of age, HR variability is lower in conscious female homozygotes relative to wild-type controls over all frequency ranges
• total HR variability is only 43% of the value in wild-type female mice
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• at 6 months of age, conscious female homozygotes exhibit a ~7% increase in heart rate relative to wild-type females (514 5 vs 481 5 beats/min, respectively)
• however, no significant differences in respiratory rate are observed
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• at 6 months of age, conscious female homozygotes show a significnat increase in BP variability within specific frequency ranges, namely the mid and high frequency bands
• specifically, the mid frequency power (0.3-0.5 Hz) corresponding to the autonomic range is 1.7 times greater while the high frequency region (0.5-1 Hz) is 2.4 times greater in female homozygotes relative to wild-type controls
• however, the overall BP variability (0-1 Hz) is not statistically different between mutant and wild-type females
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• at 6 months of age, conscious female homozygotes show a 4.5 2.0 mm Hg reduction in MAP relative to wild-type females
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• at 6 months of age, conscious female homozygotes show a lower diastolic arterial pressure than wild-type females (86.5 0.4 vs 92.6 0.5 mm Hg, respectively)
• however, no significant differences in the systolic blood pressure are observed
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cellular
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• at 1 yr of age, tubules with early spermiogenic arrest exhibit defects in early acrosomal development
• multiple acrosomal vesicles are observed and, in some cases, acrosomes fail to uniformly spread over the spermatid nuclei
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• at 1 yr of age, male homozygotes show a significant reduction in round and elongated spermatids, but no changes in Sertoli cells and earlier germ cells relative to wild-type males
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• at 1 yr of age, no significant decreases are observed in Sertoli cell numbers or in spermatogonia and spermatocyte populations; however, significantly less round and elongated spermatids are present in the mutant epithelium relative to wild-type controls
• at 4.5 months of age, the numbers of Sertoli cells, spermatogonia, spermatocytes, round spermatids, and elongated spermatids are comparable to those of wild-type males
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• at 1 yr of age, decline in round spermatid number is due to increased cell death in the adluminal compartment of the seminiferous epithelium
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• marked apoptosis in granulosa cells of larger, antral size follicles at 10-12 weeks of age
• by 1 yr of age, granulosa cell apoptosis is widespread throughout the ovary, as indicated by TUNEL analysis
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nervous system
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• at 6 months of age, the baroreflex sensitivity (BRS) in female conscious homozygotes is 46% of the value observed in wild-type females
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muscle
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• at 6 months of age, the maximum rate of change in blood pressure (dP/dT) occuring during systole is 40% higher in conscious female homozygotes relative to wild-type controls (1427 9 vs 1019 14 mm Hg/sec, respectively)
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integument
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• at 3 weeks of age, both male and female homozygotes exhibit a dull coat
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digestive/alimentary system
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• massive leukocytic infiltration with destruction of acinar cells in the salivary glands of mice fed a phytoestrogen-free diet
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• enlarged salivary glands in mice fed a phytoestrogen-free diet, although it is unclear if salivary gland/body weight ratio is normal or increased
|
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• massive leukocytic infiltration with destruction of acinar cells in the salivary glands of mice fed a phytoestrogen-free diet
• mice raised on a phytoestrogen-free diet develop Sjogren-like syndrome by 12-17 months of age, showing presence of massive infiltration of B220+ B lymphocytes, presence of an alpha-fodrin fragment (120 kDa) in the salivary gland, and higher levels of serum anti-fodrin antibody than wild-type mice fed this diet
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growth/size/body
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• hemorrhagic cystic follicles are observed by 21-23 weeks of age
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• all mice over 1 year of age develop mild splenomegaly when fed a phytoestrogen-free diet
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• splenic cellularity is increased by 2- to 4-fold in mice fed a phytoestrogen-free diet
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hematopoietic system
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• all mice over 1 year of age develop mild splenomegaly when fed a phytoestrogen-free diet
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• splenic cellularity is increased by 2- to 4-fold in mice fed a phytoestrogen-free diet
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• progressive bone marrow hyperplasia with over production of mature granulocytes and B cells in mice fed a phytoestrogen-free diet
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• number of leukocytes, particularly lymphocytes, in peripheral blood is increased by 1.5- to 2-fold in aged mice fed a phytoestrogen-free diet
• absolute number of leukocytes in the bone marrow of mice fed a phytoestrogen-free diet is more than 3-fold that in wild-type mice at 12-16 month of age
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• 2-fold increase in the percentage of granulocytes in the bone marrow of 12- to 16-month old mice fed a phytoestrogen-free diet
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• in aged mice fed a phytoestrogen-free diet
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• increase in the population of B220+ B lymphocytes in the blood of aged mice fed a phytoestrogen-free diet
• 2-fold increase in B220+ B lymphocytes in the bone marrow of 12- to 16-month old mice fed a phytoestrogen-free diet
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• the mature B cell compartment (IgM+/B220+) is increased, while the proportion of IgM+/B220- B cells is decreased in the spleen of mice fed a phytoestrogen-free diet
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• germinal center formation is seen in the spleen of mice fed a phytoestrogen-free diet, indicating immunological activation
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• aged mice fed a phytoestrogen-free diet show mild depositions of IgG in renal glomeruli, but no depositions of IgM or IgA are detected
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immune system
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• massive leukocytic infiltration with destruction of acinar cells in the salivary glands of mice fed a phytoestrogen-free diet
• mice raised on a phytoestrogen-free diet develop Sjogren-like syndrome by 12-17 months of age, showing presence of massive infiltration of B220+ B lymphocytes, presence of an alpha-fodrin fragment (120 kDa) in the salivary gland, and higher levels of serum anti-fodrin antibody than wild-type mice fed this diet
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• all mice over 1 year of age develop mild splenomegaly when fed a phytoestrogen-free diet
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• splenic cellularity is increased by 2- to 4-fold in mice fed a phytoestrogen-free diet
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• number of leukocytes, particularly lymphocytes, in peripheral blood is increased by 1.5- to 2-fold in aged mice fed a phytoestrogen-free diet
• absolute number of leukocytes in the bone marrow of mice fed a phytoestrogen-free diet is more than 3-fold that in wild-type mice at 12-16 month of age
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• 2-fold increase in the percentage of granulocytes in the bone marrow of 12- to 16-month old mice fed a phytoestrogen-free diet
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• in aged mice fed a phytoestrogen-free diet
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• increase in the population of B220+ B lymphocytes in the blood of aged mice fed a phytoestrogen-free diet
• 2-fold increase in B220+ B lymphocytes in the bone marrow of 12- to 16-month old mice fed a phytoestrogen-free diet
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• the mature B cell compartment (IgM+/B220+) is increased, while the proportion of IgM+/B220- B cells is decreased in the spleen of mice fed a phytoestrogen-free diet
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• germinal center formation is seen in the spleen of mice fed a phytoestrogen-free diet, indicating immunological activation
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• aged mice fed a phytoestrogen-free diet show mild depositions of IgG in renal glomeruli, but no depositions of IgM or IgA are detected
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• all mice over 1 year of age develop lymphoadenopathy when fed a phytoestrogen-free diet
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• mice fed a phytoestrogen-free diet have autoantibodies against filamentous cytoskeletal proteins
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• kidneys of mice fed a phytoestrogen-free diet show massive infiltration of B lymphocytes, many of which are plasma cells
• however, glomerulonephritis is not seen in aged mice
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renal/urinary system
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• in mice fed a phytoestrogen-free diet
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• kidneys of mice fed a phytoestrogen-free diet show massive infiltration of B lymphocytes, many of which are plasma cells
• however, glomerulonephritis is not seen in aged mice
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• aged mice fed a phytoestrogen-free diet show mild depositions of IgG in renal glomeruli
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Sjogren's syndrome | DOID:12894 |
OMIM:270150 |
J:92438 | |
