Analysis Tools
behavior/neurological
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• male mice showed a decrease in aggressive behavior relative to wild-type
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• in a resident intruder assay aggressive behaviors toward the intruder male are greatly reduced
• loss of offensive attacks is also seen when males are tested in a neutral cage
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• gonadally intact females exhibit higher levels of aggression toward gonadectomized and steroid-primed female intruders, however gonadectomized mutant females do not show increased aggression
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hyperactivity
(
J:38600
)
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• male mice exhibited female-type open field behavior including increased activity
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• male mice exhibited female-type open field behavior including increased rearing
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• gondadally intact and gonadectomized females showed greatly reduced levels of parental behavior toward newborn pups placed in their home cage
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• noninfanticidal female mutants displayed reduced levels of retrieving behavior
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• about 40% of mutant females displayed infanticidal behavior
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• males housed overnight with hormone-primed wild-type females produced significantly fewer copulatory plugs than heterozygous or wild-type males
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• males mounted females but made fewer intromissions
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• gonadectomized females showed rejections toward male sexual behavior about 80% of the time
(J:51468)
• estrogen or estrogen plus progesterone-treated gonadectomized females showed prereceptive posture but did not display lordosis behavior
(J:51468)
• females fail to show lordosis posture or receptiveness to wild-type males even when treated with estrogen
(J:16338)
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reproductive system
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• the sperm motility of 8-16-wk-old males declines from 20% to less than 1% during a 90-min period of in vitro capacitation
• mutant sperm beat less vigorously and display less forward progression than wild-type sperm
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• containing few granulosa cells
• hyperemic cystic ovaries
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• hemorrhagic ovarian cysts
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• the lumen of the rete testis became significantly dilated at 60 days after birth
• however, the efferent ductules and epididymides showed no signs of dilation or dysmorphology in young or adult mice
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• by 20-24 weeks of age, seminiferous tubules either had a dilated lumen and a thin layer of Sertoli cells or a disorganized epithelium with few spermatogonia or lacked a lumen and contained mostly Sertoli cells
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• at 20 days after birth, the seminiferous epithelium is thinner than normal
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• at 20 days after birth, the lumen of seminiferous tubules was significantly dilated
• tubule dilation progressed with age and became more pronounced at 60 days after birth
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• degenerating seminiferous tubules were observed beginning at 10 to 12 weeks of age
• degeneration was initiated at the caudal pole of the testis and progressed in a wave to the cranial pole between 3-6 months of age
• only a few partially intact tubules were noted at the cranial pole at 6 months of age
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(J:16338)
• at 20-23 weeks of age, the weight of mutant testis was significantly lower than that of wild-type or heterozygous males
(J:36658)
• in contrast, the weights of the seminal glands, coagulating glands, and epididymi remained normal at 5-6 months of age
(J:36658)
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• the percentage area of the uterus innervated by PGP 9.5 and DBH immunoreactive nerves is increased even when normalized for the decrease in uterine size
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• endometrial stroma is less dense, approaching a mesh like morphology in extreme cases
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small uterus
(
J:85911
)
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• at 118 days of age
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• stromal, epithelial, and myometrial tissue compartments are all reduced
• however, all major cell types are present
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• disruption of spermatogenesis evident after 10 weeks of age
• spermatogenesis occurs in the seminiferous tubules of some mutants at 3-5 months of age
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• sperm count was 10% that of wild-type
(J:16338)
• a reduced concentration of epididymal sperm was noted in the caput region at 10 weeks of age, and in more distal regions at 20 weeks of age
(J:36658)
• sperm counts declined and became significantly lower than those of wild-type controls by 12-13 weeks of age
(J:36658)
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• sperm with retroflexed bending in the midpiece region were commonly observed
• however, no major sperm head abnormalities were found to occur
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• sperm heads were commonly detached from the flagellum
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• by 20-24 weeks of age, epididymides were often hypospermic esp. in the caput and corpus regions
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• females fail to respond to estrogen treatment
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• males sired no offspring during a 2-month mating period
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• 3 of 15 males sired offspring
• males that did not sire offspring also did not produce vaginal plugs
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• sperm from 8-16-wk-old male mutants display a significantly reduced in vitro fertilization capacity relative to wild-type sperm
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• when placed with a receptive female for 90 min, males display mounts and intromissions but fail to ejaculate
(J:66582)
• ejaculations were never observed in mutants
(J:38600)
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homeostasis/metabolism
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• at 20-23 weeks of age, serum testosterone levels are moderately increased relative to wild-type and heterozygous levels
• in contrast, serum LH and FSH levels are slightly but not significantly increased
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• about a 10 fold increase in 17beta estradiol levels in females
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• levels are 23% lower than in wild-type controls at 118 days of age
(J:114164)
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• in males at 4 months of age but not at 1 or 2 months of age
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• decrease in the concentration of osteocalcin, a marker of bone formation, in the serum at 110 days of age
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• in adult males
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• in adult males
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• in males at 4 months of age the insulin x free fatty acid product is increased suggesting the mice are insulin resistant
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• in males and females at 1 year of age
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• 17beta-estradiol-treated castrated mice fail to exhibit a decrease in bone marrow cellularity, immunoglobulin switching, or increased production of immunoglobulins (IgA, IgG, and IgM) and exhibit a reduced decrease in the frequency of B cells unlike similarly treated wild-type mice
• 17beta-estradiol-treated castrated mice fail to exhibit a decrease in pre-B cells and newly formed B cells unlike similarly treated wild-type mice
• however, 17beta-estradiol-treated castrated mice exhibit a decrease in pro-B cell
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cardiovascular system
growth/size/body
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• hemorrhagic ovarian cysts
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• late pubertal and young adult body weight is decreased compared to controls
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• in adult mice (over 44 days of age)
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respiratory system
skeleton
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• unlike for the appendicular skeleton, no difference in the length of the axial skeleton is detected
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short ulna
(
J:91765
)
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• ulnae are 4% shorter and straighter than in wild-type mice
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• in post-pubertal mice
(J:62222)
• at 118 days of age but not at 31 or 65 days of age
(J:114164)
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short tibia
(
J:114164
)
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• at 118 days of age but not at 31 or 65 days of age
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• bone mineral content normalized to body weight is decreased in the total body, femur and spine
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• total areal bone mineral density is slightly decreased in adults
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• femur bone mineral density is decreased in adults
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• decrease in mid-diaphyseal bone mineral content in the femur and tibia mainly as a result of a decrease in cross-sectional area associated with a decrease in periosteal and endosteal circumference
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• under non-loading condition, cortical area is 12% greater than in wild-type mice
• load-induced increase in cortical area is reduced 3-fold compared to in similarly treated wild-type mice
• under non-loading condition, periosteal perimeter is 6% greater than in wild-type mice
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• after 10 minutes of mechanical stress, the number of osteoblast-like cells is decreased unlike in similarly treated wild-type mice
• however, transfection of the endogenous gene restores the increase in load-induced osteoblast cells to levels greater than in similarly treated wild-type mice
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• under non-loading condition, mice exhibit reduced endosteal mineralizing surface compared with wild-type mice
• load-induced increase in periosteal mineralization is decreased 40% compared to in similarly treated wild-type mice
• load-induced endosteal mineral apposition rate is 50% lower than in similarly treated wild-type mice
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• under non-loading condition, mice exhibit reduced bone formation compared with wild-type mice
• load-induced periosteal and endosteal bone formation rates are 60% lower than in similarly treated wild-type mice
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• decrease in maximal load
• however, other parameters, such as maximal stress and elastic modulus, are not significantly different from controls
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embryo
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• at P23 the efferent ductules are enlarged and dilated in females
• in adult females well developed and enlarged ductules with occasional epididymal-like initial segments are seen
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immune system
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• 17beta-estradiol-treated castrated mice fail to exhibit immunoglobulin switching unlike similarly treated wild-type mice
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• mice have increased double positive CD4+CD8+ thymocytes compared to 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 pre-B cells and newly formed B cells unlike similarly treated wild-type mice
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• display plasmacytosis of the spleen and kidney
• lymph nodes also display an accumulation of plasma cells
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• mice have fewer single positive CD4+ and CD8+ thymocytes compared to in wild-type mice
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• mice have fewer single positive CD4+ and CD8+ thymocytes compared to in wild-type mice
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• despite being kept in a specific pathogen free environment mice spontaneously develop germinal centers
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• 17beta-estradiol-treated castrated mice fail to exhibit an increase in production of immunoglobulins (IgA, IgG, and IgM) compared with similarly treated wild-type mice
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• in females
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• display an accumulation of plasma cells
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• display plasmacytosis of the spleen
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• in males and females
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• seen in males and females by 1 year of age
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renal/urinary system
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• in males and females at 1 year of age
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• show some degree of mesangial sclerosis at 1 year of age
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• deposits of IgG are detected in the glomeruli
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• display plasmacytosis of the kidney
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• seen in males and females by 1 year of age
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nervous system
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• in the anteroventral periventricular nucleus the number of TH positive neurons is increased in males compared to wild-type males
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• the percentage area of the uterus innervated by PGP 9.5 and DBH immunoreactive nerves is increased even when normalized for the decrease in uterine size
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adipose tissue
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• in males at 4 months of age but not at 1 or 2 months of age
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• in males at 4 months of age
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• in males at 4 months of age
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endocrine/exocrine glands
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• containing few granulosa cells
• hyperemic cystic ovaries
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• hemorrhagic ovarian cysts
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• the lumen of the rete testis became significantly dilated at 60 days after birth
• however, the efferent ductules and epididymides showed no signs of dilation or dysmorphology in young or adult mice
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• by 20-24 weeks of age, seminiferous tubules either had a dilated lumen and a thin layer of Sertoli cells or a disorganized epithelium with few spermatogonia or lacked a lumen and contained mostly Sertoli cells
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• at 20 days after birth, the seminiferous epithelium is thinner than normal
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• at 20 days after birth, the lumen of seminiferous tubules was significantly dilated
• tubule dilation progressed with age and became more pronounced at 60 days after birth
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• degenerating seminiferous tubules were observed beginning at 10 to 12 weeks of age
• degeneration was initiated at the caudal pole of the testis and progressed in a wave to the cranial pole between 3-6 months of age
• only a few partially intact tubules were noted at the cranial pole at 6 months of age
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(J:16338)
• at 20-23 weeks of age, the weight of mutant testis was significantly lower than that of wild-type or heterozygous males
(J:36658)
• in contrast, the weights of the seminal glands, coagulating glands, and epididymi remained normal at 5-6 months of age
(J:36658)
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limbs/digits/tail
short ulna
(
J:91765
)
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• ulnae are 4% shorter and straighter than in wild-type mice
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• in post-pubertal mice
(J:62222)
• at 118 days of age but not at 31 or 65 days of age
(J:114164)
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short tibia
(
J:114164
)
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• at 118 days of age but not at 31 or 65 days of age
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hematopoietic system
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• 17beta-estradiol-treated castrated mice fail to exhibit immunoglobulin switching unlike similarly treated wild-type mice
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• mice have increased double positive CD4+CD8+ thymocytes compared to 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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• 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 pre-B cells and newly formed B cells unlike similarly treated wild-type mice
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• display plasmacytosis of the spleen and kidney
• lymph nodes also display an accumulation of plasma cells
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• mice have fewer single positive CD4+ and CD8+ thymocytes compared to in wild-type mice
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• mice have fewer single positive CD4+ and CD8+ thymocytes compared to in wild-type mice
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• despite being kept in a specific pathogen free environment mice spontaneously develop germinal centers
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• 17beta-estradiol-treated castrated mice fail to exhibit an increase in production of immunoglobulins (IgA, IgG, and IgM) compared with similarly treated wild-type mice
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• in females
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cellular
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• sperm count was 10% that of wild-type
(J:16338)
• a reduced concentration of epididymal sperm was noted in the caput region at 10 weeks of age, and in more distal regions at 20 weeks of age
(J:36658)
• sperm counts declined and became significantly lower than those of wild-type controls by 12-13 weeks of age
(J:36658)
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• sperm with retroflexed bending in the midpiece region were commonly observed
• however, no major sperm head abnormalities were found to occur
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• sperm heads were commonly detached from the flagellum
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• the sperm motility of 8-16-wk-old males declines from 20% to less than 1% during a 90-min period of in vitro capacitation
• mutant sperm beat less vigorously and display less forward progression than wild-type sperm
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