Phenotypes Associated with This Genotype

Genotype
MGI:3688155

• Allelic Composition: Esr1^tm1Ksk/Esr1^tm1Ksk
• Genetic Background: involves: 129P2/OlaHsd

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

reproductive system

ovary hemorrhage ( J:55147 , J:64639 )

♀ • hemorrhagic ovarian follicles (J:55147)

♀ • atretic hemorrhagic follicular cysts (J:64639)

oligozoospermia ( J:60490 )

♂ • cauda epididymides show a reduced concentration of sperm

abnormal ovary morphology ( J:64639 )

♀

absent corpus luteum ( J:55147 , J:64639 )

♀ (J:55147)

♀ • in untreated females (J:64639)

♀ • however, females grafted with a heterozygous pituitary gland display hypertrophied luteal cells that are highly vacuolated with lipid droplets indicating steroidogenesis (J:64639)

impaired ovarian folliculogenesis ( J:55147 )

♀ • follicles develop to the large antral stage but fail to progress further

♀ • antral stage follicles contain apoptotic granulosa cells and degenerating oocytes

ovarian follicular cyst ( J:55147 , J:64639 , J:72221 )

♀ (J:55147)

♀ • atretic hemorrhagic follicular cysts (J:64639)

♀ (J:72221)

decreased uterus weight ( J:72221 , J:152738 )

♀ • in untreated mice (J:72221)

♀ • however, mice do not display diethylstilbestrol (DES) induced reduction in uterine weight (J:72221)

♀ (J:152738)

uterus hypoplasia ( J:72221 )

♀

abnormal vagina epithelium morphology ( J:72221 )

♀ • epithelium is not cornified

abnormal internal male genitalia morphology ( J:112350 )

♂ • descended testes are higher in the cremaster sac compared to wild-type littermates

♂ • the cremaster sac is smaller in length and width and has a much thicker layer of cremaster muscle

abnormal testis morphology ( J:60490 , J:112350 )

♂ • mutants exhibit glycogen-containing cells at the rete testis-efferent ductile junction (J:60490)

♂ • at 21 to 25 weeks of age in 4 males 6 of 8 testis were retracted up to near the bladder neck (J:112350)

♂ • however, external examination did not reveal any defect in testicular descent (J:112350)

dilated rete testis ( J:83231 , J:125658 )

♂ (J:83231)

♂ • dilated rete testis compared to wild-type (J:125658)

seminiferous tubule degeneration ( J:112350 )

♂ • degenerate, empty tubules

abnormal testis weight ( J:83231 )

♂ • transient increase in testis weight between 32 and 81 days of age and a decrease by 185 days

♂ • after ductal occlusion testes of mutants weigh 30% more than wild-type, due to luminal fluid accumulation

abnormal efferent ductules of testis morphology ( J:60490 )

♂ • increase in the prevalence of blind-ending efferent tubules; these blind-ending tubules have an empty and collapsaed lumen, and epithelial cells contain fewer cytoplasmic organelles, particularly lysosomes and endocytotic vesicles

♂ • the blind-ending tubules often contain enlarged bulbous endings that are never seen in wild-type

♂ • efferent ductule epithelial height is reduced by 48%

♂ • number of cilia per epithelial cell is reduced and the cilia do not show the typical parallel arrangement

♂ • microvilli of nonciliated cells of efferent ductules along the apical border are often missing and when present, are 64% shorter in length

♂ • nonciliated cells have missing or greatly reduced endocytotic apparatus

dilated efferent ductule of testis ( J:60490 , J:83231 , J:125658 )

♂ • efferent tubules are dilated between 130 to 300% over wild-type ductules (J:60490)

♂ • efferent ductules are swollen, with luminal areas more than twice the size of wild-type males (J:83231)

♂ (J:125658)

abnormal epididymis morphology ( J:60490 )

♂ • increase in the prevalence of blind-ending efferent tubules

♂ • tubular diameters of the initial segment epididymides are dilated

♂ • apical, narrow, and clear cells of the epididymis are abnormal in some regions

spermatic granuloma ( J:60490 )

♂ • sperm granulomas are seen in the corpus and cauda regions of 1/3 of mutant males

abnormal epididymis epithelium morphology ( J:60490 , J:83231 )

♂ • initial segment epithelium is displaced into regions adjacent to the rete tesis and in short segments of the common region of efferent ductule (J:60490)

♂ • endocytotic vesicles and large PAS+ lysosomal granules are reduced or missing in the epithelium of the epididymis (J:83231)

♂ • epididymal epithelium is decreased in height by 45% (J:83231)

anovulation ( J:64639 )

♀

failure of superovulation ( J:55147 )

♀ • treatment with exogenous pregnant mare serum gonadotropin followed by human chorionic gonadotropin fails to induce ovulation

failure of embryo implantation ( J:108638 )

♀ • transplanted wild-type embryos fail to implant in ovariectomized hormone treated females

♀ • nodules that do form contain only decidualized uterine tissue

abnormal male reproductive system physiology ( J:83231 )

♂ • after unilateral occlusion, rete testes secretes significantly less fluid in 24 hours than wild-type

♂ • efferent ductules from mutants treated with an anti-estorgen compound are incapable of reabsorbing luminal fluid while wild-type ductules remove most of the fluid within 3 hours

male infertility ( J:125658 )

♂ • males are sterile

cellular

oligozoospermia ( J:60490 )

♂ • cauda epididymides show a reduced concentration of sperm

nervous system

decreased lactotroph cell number ( J:40607 )

• modest decrease in lactotroph cell density

abnormal pituitary gland physiology ( J:40607 )

• patterns of staining for a gonadotropin subunit proteins are altered

hematopoietic system

hematopoietic system phenotype ( J:110923 )

N • despite absence of Esr1, cultured bone marrow stromal cells respond to estrogen to depress B cell precursor expansion

decreased immature B cell number ( J:110923 )

• decrease in the percentage of CD45R+, sIgM+ B cells in the bone marrow

abnormal bone marrow cell number ( J:110923 )

• decrease in the percentages of mature and CD45R+, sIgM+ B cells in the bone marrow

decreased mature B cell number ( J:110923 )

• decrease in the percentage of mature B cells in the bone marrow

homeostasis/metabolism

increased circulating glucose level ( J:151012 )

decreased circulating testosterone level ( J:152738 )

• in ovariectomized female mice

increased circulating testosterone level ( J:152738 )

• 8 times higher in female mice compared with wild-type mice

decreased circulating estradiol level ( J:152738 )

• in ovariectomized female mice

increased circulating estradiol level ( J:72221 )

decreased circulating prolactin level ( J:64639 )

• in adult females

• in ovariectomized females treated with estradiol prolactin levels remain low unlike in wild-type mice

impaired glucose tolerance ( J:151012 )

• prior to and after tamoxifen treatment

insulin resistance ( J:151012 )

• mice exhibit insulin resistance compared with wild-type mice

• treatment with tamoxifen increases insulin sensitivity but mice remain insulin resistant compared with wild-type mice 15 and 30 minutes after treatment

• however, tamoxifen-treatment eventually restores normal insulin sensitivity

albuminuria ( J:152738 )

• around 7 to 8 months, female mice exhibit increased albumin excretion compared with wild-type mice

• however, male mice and ovariectomized female mice exhibit normal albumin excretion

abnormal response/metabolism to endogenous compounds ( J:131313 , J:152738 )

• thymic atrophy induced by E2 treatment is attenuated compared to in similarly treated wild type mice (J:131313)

• E2 induced accumulation of DN1 and reduction of DN2 thymocytes is completely abrogated compared to in wild-type mice (J:131313)

• following treatment with 17beta-estradiol, female mice does not exhibit an increase in uterine weight unlike similarly treated wild-type mice (J:152738)

abnormal physiological response to xenobiotic ( J:135833 )

• treatment with PPT (propyl(1H) pyrazole-1,3,5-triyl-trisphenol) protects mice from accoustic trauma unlike similarly treated wild-type mice

decreased physiological sensitivity to xenobiotic ( J:72221 )

• do not display diethylstilbestrol (DES) induced reduction in uterine weight, increase in body weight, or pathological changes in reproductive tissues

cardiovascular system

cardiovascular system phenotype ( J:163783 )

N • mice exhibit normal estrogen- and estrogen-dendrimer conjugate (EDC)-induced reendothelialization following arterial denudation

ovary hemorrhage ( J:55147 , J:64639 )

♀ • hemorrhagic ovarian follicles (J:55147)

♀ • atretic hemorrhagic follicular cysts (J:64639)

muscle

abnormal cremaster muscle morphology ( J:112350 )

♂ • the cremaster sac is smaller in length and width and has a much thicker layer of cremaster muscle

♂ • cross sectional width of the cremaster muscle at its abdominal wall attachment and at its tip is about twice that of wild-type controls

immune system

decreased immature B cell number ( J:110923 )

• decrease in the percentage of CD45R+, sIgM+ B cells in the bone marrow

decreased mature B cell number ( J:110923 )

• decrease in the percentage of mature B cells in the bone marrow

spermatic granuloma ( J:60490 )

♂ • sperm granulomas are seen in the corpus and cauda regions of 1/3 of mutant males

endocrine/exocrine glands

ovary hemorrhage ( J:55147 , J:64639 )

♀ • hemorrhagic ovarian follicles (J:55147)

♀ • atretic hemorrhagic follicular cysts (J:64639)

decreased lactotroph cell number ( J:40607 )

• modest decrease in lactotroph cell density

abnormal mammary gland development ( J:64639 )

♀ • only a rudimentary ductal structure is present

♀ • in ovariectomized females treated with estradiol mammary glands do not exhibit any growth

♀ • restoring prolactin levels by grafting half a heterozygous pituitary gland induces dramatic mammary gland growth in ovary intact females

♀ • hormone treatment with estradiol and progesterone stimulates ductal branching and lobuloalveolar development and terminal end bud formation

abnormal ovary morphology ( J:64639 )

♀

absent corpus luteum ( J:55147 , J:64639 )

♀ (J:55147)

♀ • in untreated females (J:64639)

♀ • however, females grafted with a heterozygous pituitary gland display hypertrophied luteal cells that are highly vacuolated with lipid droplets indicating steroidogenesis (J:64639)

impaired ovarian folliculogenesis ( J:55147 )

♀ • follicles develop to the large antral stage but fail to progress further

♀ • antral stage follicles contain apoptotic granulosa cells and degenerating oocytes

ovarian follicular cyst ( J:55147 , J:64639 , J:72221 )

♀ (J:55147)

♀ • atretic hemorrhagic follicular cysts (J:64639)

♀ (J:72221)

abnormal testis morphology ( J:60490 , J:112350 )

♂ • mutants exhibit glycogen-containing cells at the rete testis-efferent ductile junction (J:60490)

♂ • at 21 to 25 weeks of age in 4 males 6 of 8 testis were retracted up to near the bladder neck (J:112350)

♂ • however, external examination did not reveal any defect in testicular descent (J:112350)

dilated rete testis ( J:83231 , J:125658 )

♂ (J:83231)

♂ • dilated rete testis compared to wild-type (J:125658)

seminiferous tubule degeneration ( J:112350 )

♂ • degenerate, empty tubules

abnormal testis weight ( J:83231 )

♂ • transient increase in testis weight between 32 and 81 days of age and a decrease by 185 days

♂ • after ductal occlusion testes of mutants weigh 30% more than wild-type, due to luminal fluid accumulation

abnormal pituitary gland physiology ( J:40607 )

• patterns of staining for a gonadotropin subunit proteins are altered

growth/size/body

ovarian follicular cyst ( J:55147 , J:64639 , J:72221 )

♀ (J:55147)

♀ • atretic hemorrhagic follicular cysts (J:64639)

♀ (J:72221)

increased body weight ( J:72221 , J:152738 )

• in untreated females (J:72221)

• however, mice do not display diethylstilbestrol (DES) induced increase in body weight (J:72221)

• in female mice (J:152738)

decreased body length ( J:111108 )

• at 9 and 18 months, crown to rump length is decreased compared to Esr1^tm1Ksk Esr2^tm1Unc homozygotes

limbs/digits/tail

short femur ( J:111108 )

• at 4, 9, and 18 months, femur length is decreased compared to in Esr1^tm1Ksk Esr2^tm1Unc homozygotes

skeleton

short femur ( J:111108 )

• at 4, 9, and 18 months, femur length is decreased compared to in Esr1^tm1Ksk Esr2^tm1Unc homozygotes

abnormal vertebrae morphology ( J:111108 )

• at 18 months, vertebra height is decreased compared to in Esr1^tm1Ksk Esr2^tm1Unc homozygotes

abnormal skeleton development ( J:111108 )

• at 4 months, femur growth velocity is reduced compared to in wild-type mice

abnormal long bone epiphyseal plate morphology ( J:111108 )

• at 18 months, the growth plates in the femur and tibia are fused unlike in wild-type mice

• column density is decreased compared to in Esr1^tm1Ksk Esr2^tm1Unc homozygotes

decreased long bone epiphyseal plate size ( J:111108 )

• at 4 months, the femur growth plate exhibit decreased height compared to in wild-type mice

• at 18 months, the tibia and femur growth plates exhibit decreased height compared to in wild-type mice

abnormal chondrocyte physiology ( J:111108 )

• chondrocyte proliferation in the femur is increased compared to in Esr1^tm1Ksk Esr2^tm1Unc homozygotes

• however, chondrocyte proliferation in the tibia and vertebra is normal

renal/urinary system

albuminuria ( J:152738 )

• around 7 to 8 months, female mice exhibit increased albumin excretion compared with wild-type mice

• however, male mice and ovariectomized female mice exhibit normal albumin excretion

expanded mesangial matrix ( J:152738 )

• female mice exhibit diffuse mesangial matrix expansion compared with wild-type mice

renal glomerulus hypertrophy ( J:152738 )

• at 9 months, female mice exhibit an increase in glomerular size compared with wild-type mice

• however, ovariectomized female mice exhibit normal glomerular size

integument

abnormal mammary gland development ( J:64639 )

♀ • only a rudimentary ductal structure is present

♀ • in ovariectomized females treated with estradiol mammary glands do not exhibit any growth

♀ • restoring prolactin levels by grafting half a heterozygous pituitary gland induces dramatic mammary gland growth in ovary intact females

♀ • hormone treatment with estradiol and progesterone stimulates ductal branching and lobuloalveolar development and terminal end bud formation