All Phenotypes Esr1<tm1Ksk> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Esr1^tm1Ksk/Esr1^tm1Ksk	B6.129P2-Esr1^tm1Ksk	MGI:4398702
hm2	Esr1^tm1Ksk/Esr1^tm1Ksk	B6.129P2-Esr1^tm1Ksk/J	MGI:3839858
hm3	Esr1^tm1Ksk/Esr1^tm1Ksk	involves: 129P2/OlaHsd	MGI:3688155
hm4	Esr1^tm1Ksk/Esr1^tm1Ksk	involves: 129P2/OlaHsd * 129S6/SvEvTac	MGI:4418904
hm5	Esr1^tm1Ksk/Esr1^tm1Ksk	involves: 129P2/OlaHsd * C57BL/6	MGI:4398705
hm6	Esr1^tm1Ksk/Esr1^tm1Ksk	involves: 129P2/OlaHsd * C57BL/6J	MGI:2664581
hm7	Esr1^tm1Ksk/Esr1^tm1Ksk	involves: 129P2/OlaHsd * C57BL/6N	MGI:4398704
hm8	Esr1^tm1Ksk/Esr1^tm1Ksk	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:4437741
ht9	Esr1^tm1Ksk/Esr1⁺	involves: 129P2/OlaHsd	MGI:4398701
cx10	Apoe^tm1Bres/Apoe^tm1Bres Esr1^tm1Ksk/Esr1^tm1Ksk	B6.129P2-Apoe^tm1Bres Esr1^tm1Ksk	MGI:4437892
cx11	Esr1^tm1Ksk/Esr1^tm1Ksk Esr2^tm1Unc/Esr2^tm1Unc	involves: 129P2/OlaHsd	MGI:2664687
cx12	Esr1^tm1Ksk/Esr1^tm1Ksk Esr2^tm1Unc/Esr2^tm1Unc Inha^tm1Bay/Inha⁺	involves: 129P2/OlaHsd * 129S6/SvEvTac * 129S7/SvEvBrd	MGI:4418903
cx13	Esr1^tm1Ksk/Esr1^tm1Ksk Inha^tm1Bay/Inha^tm1Bay	involves: 129P2/OlaHsd * 129S6/SvEvTac * 129S7/SvEvBrd	MGI:4418905
cx14	Esr1^tm1Ksk/Esr1^tm1Ksk Esr2^tm1Unc/Esr2^tm1Unc Inha^tm1Bay/Inha^tm1Bay	involves: 129P2/OlaHsd * 129S6/SvEvTac * 129S7/SvEvBrd	MGI:4418901
cx15	Esr1^tm1Ksk/Esr1^tm1Ksk Esr2^tm1Unc/Esr2^tm1Unc	involves: 129P2/OlaHsd * C57BL/6J	MGI:4398703
cx16	Esr1^tm1Ksk/Esr1^tm1Ksk Tg(MMTV-Erbb2)NK1Mul/0	involves: 129P2/OlaHsd * C57BL/6J * FVB/N	MGI:4438040
cx17	Esr1^tm1Ksk/Esr1^tm1Ksk Tg(Wnt1)1Hev/0	involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:4437739

Allelic Composition	Esr1^tm1Ksk/Esr1^tm1Ksk
Genetic Background	B6.129P2-Esr1^tm1Ksk

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Esr1^tm1Ksk mutation (2 available); any Esr1 mutation (68 available)

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

adipose tissue

adipose tissue phenotype ( J:65806 )

N	• no significant difference in the amount of brown adipose tissue is detected in male or females at any age

increased white adipose tissue amount ( J:65806 )

• progressive increase in the amount of white adipose tissue with age in males

increased white fat cell number ( J:65806 )

• at 180 days of age the numbers of adipocytes in the perirenal and epididymal fat pads are significantly increased

• at 90 days of age the number of adipocytes is increased in females

increased white fat cell size ( J:65806 )

• at 180 days of age the areas of adipocytes from the perirenal and epididymal fat pads are significantly increased

• at 90 days of age the size of adipocytes is increased in females

increased epididymal fat pad weight ( J:65806 )

• in males at 30 and 90 days of age

increased inguinal fat pad weight ( J:65806 )

• in males and females at 90 days of age

increased renal fat pad weight ( J:65806 )

• in males at between 270 and 360 days of age

• in females at 90 days of age

increased parametrial fat pad weight ( J:65806 )

• at 90 days of age

homeostasis/metabolism

decreased energy expenditure ( J:65806 )

• in males compared to wild-type littermate controls

impaired glucose tolerance ( J:65806 )

• glucose levels are higher at 30, 60 and 120 min after a glucose challenge in males compared to similarly treated wild-type males

• glucose tolerance is also impaired in females

insulin resistance ( J:65806 )

• following a glucose challenge insulin levels are significantly increased in males and females compared to wild-type controls

behavior/neurological

behavior/neurological phenotype ( J:65806 )

N	• no increase in food intake is seen despite the increase in the amount of white adipose tissue

impaired passive avoidance behavior ( J:65785 )

• retention is impaired in an inhibitory avoidance assay

• treatment with estradiol improves retention to a level similar to that in estradiol treated wild-type controls

hyporesponsive to tactile stimuli ( J:151022 )

• female mice exhibit an increased threshold to mechanical nociception compared with similarly treated wild-type female mice

• however, male mice exhibit normal mechanical nociception

abnormal nociception after inflammation ( J:151022 )

• female mice exhibit an increased threshold to mechanical nociception following inflammation compared with similarly treated wild-type female mice

• however, male mice exhibit normal mechanical nociception after inflammation

growth/size/body

decreased birth weight ( J:65806 )

• in males

increased body weight ( J:65806 )

• by 11 months of age males weigh 16% more than wild-type males

Allelic Composition	Esr1^tm1Ksk/Esr1^tm1Ksk
Genetic Background	B6.129P2-Esr1^tm1Ksk/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Esr1^tm1Ksk mutation (2 available); any Esr1 mutation (68 available)

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

reproductive system

oligozoospermia ( J:147000 )

• in some mice

seminiferous tubule degeneration ( J:147000 )

• in some mice

endocrine/exocrine glands

seminiferous tubule degeneration ( J:147000 )

• in some mice

cellular

oligozoospermia ( J:147000 )

• in some mice

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Esr1^tm1Ksk mutation (2 available); any Esr1 mutation (68 available)

♀	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

Allelic Composition	Esr1^tm1Ksk/Esr1^tm1Ksk
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Esr1^tm1Ksk mutation (2 available); any Esr1 mutation (68 available)

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

reproductive system

dilated seminiferous tubule ( J:84989 )

homeostasis/metabolism

increased circulating estradiol level ( J:84989 )

endocrine/exocrine glands

dilated seminiferous tubule ( J:84989 )

Allelic Composition	Esr1^tm1Ksk/Esr1^tm1Ksk
Genetic Background	involves: 129P2/OlaHsd * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Esr1^tm1Ksk mutation (2 available); any Esr1 mutation (68 available)

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

cardiovascular system

abnormal response of heart to induced stress ( J:62353 )

• following induced ischemia hearts take longer to resume regular beating, produce more nitrite, accumulate more calcium, reduce less MTT indicting a more severe impairment of mitochondrial respiratory function, and show more extensive and intense cellular damage

homeostasis/metabolism

abnormal response of heart to induced stress ( J:62353 )

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

behavior/neurological

decreased aggression ( J:38600 )

• male mice showed a decrease in aggressive behavior relative to wild-type

decreased aggression towards male mice ( J:66582 )

• 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

increased aggression towards female mice ( J:51468 )

• gonadally intact females exhibit higher levels of aggression toward gonadectomized and steroid-primed female intruders, however gonadectomized mutant females do not show increased aggression

hyperactivity ( J:38600 )

• male mice exhibited female-type open field behavior including increased activity

increased vertical activity ( J:38600 )

• male mice exhibited female-type open field behavior including increased rearing

abnormal maternal nurturing ( J:51468 )

• gondadally intact and gonadectomized females showed greatly reduced levels of parental behavior toward newborn pups placed in their home cage

abnormal pup retrieval ( J:51468 )

• noninfanticidal female mutants displayed reduced levels of retrieving behavior

pup cannibalization ( J:51468 )

• about 40% of mutant females displayed infanticidal behavior

decreased copulatory plug deposition ( J:36658 )

• males housed overnight with hormone-primed wild-type females produced significantly fewer copulatory plugs than heterozygous or wild-type males

abnormal intromission ( J:38600 )

• males mounted females but made fewer intromissions

reduced male mating frequency ( J:51468 )

abnormal mating receptivity ( J:16338 , J:51468 )

• females fail to show lordosis posture or receptiveness to wild-type males even when treated with estrogen (J:16338)

• 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)

reproductive system

asthenozoospermia ( J:36658 )

• 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

abnormal ovary morphology ( J:16338 )

• containing few granulosa cells

• hyperemic cystic ovaries

absent corpus luteum ( J:16338 )

ovarian follicular cyst ( J:16338 )

• hemorrhagic ovarian cysts

dilated rete testis ( J:36658 )

• 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

abnormal seminiferous tubule morphology ( J:36658 )

• 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

abnormal seminiferous tubule epithelium morphology ( J:36658 )

• at 20 days after birth, the seminiferous epithelium is thinner than normal

dilated seminiferous tubule ( J:36658 )

• 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

seminiferous tubule degeneration ( J:36658 )

• 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

decreased testis weight ( J:16338 , J:36658 )

(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)

abnormal uterus morphology ( J:85911 )

• 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

abnormal endometrium morphology ( J:85911 )

• endometrial stroma is less dense, approaching a mesh like morphology in extreme cases

small uterus ( J:85911 )

decreased uterus weight ( J:114164 )

• at 118 days of age

uterus hypoplasia ( J:16338 )

• stromal, epithelial, and myometrial tissue compartments are all reduced

• however, all major cell types are present

abnormal spermatogenesis ( J:36658 )

• disruption of spermatogenesis evident after 10 weeks of age

• spermatogenesis occurs in the seminiferous tubules of some mutants at 3-5 months of age

oligozoospermia ( J:16338 , J:36658 )

• 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)

teratozoospermia ( J:36658 )

• sperm with retroflexed bending in the midpiece region were commonly observed

• however, no major sperm head abnormalities were found to occur

detached sperm flagellum ( J:36658 )

• sperm heads were commonly detached from the flagellum

abnormal epididymis morphology ( J:36658 )

• by 20-24 weeks of age, epididymides were often hypospermic esp. in the caput and corpus regions

abnormal female reproductive system physiology ( J:16338 )

• females fail to respond to estrogen treatment

female infertility ( J:16338 )

male infertility ( J:36658 )

• males sired no offspring during a 2-month mating period

reduced male fertility ( J:16338 )

• 3 of 15 males sired offspring

• males that did not sire offspring also did not produce vaginal plugs

impaired fertilization ( J:36658 )

• sperm from 8-16-wk-old male mutants display a significantly reduced in vitro fertilization capacity relative to wild-type sperm

failure of ejaculation ( J:38600 , J:66582 )

• ejaculations were never observed in mutants (J:38600)

• when placed with a receptive female for 90 min, males display mounts and intromissions but fail to ejaculate (J:66582)

homeostasis/metabolism

increased circulating testosterone level ( J:36658 )

• 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

increased circulating estradiol level ( J:112080 )

• about a 10 fold increase in 17beta estradiol levels in females

decreased circulating insulin-like growth factor I level ( J:62222 , J:114164 )

• levels are 23% lower than in wild-type controls at 118 days of age (J:114164)

increased circulating leptin level ( J:66077 )

• in males at 4 months of age but not at 1 or 2 months of age

decreased circulating osteocalcin level ( J:62222 )

• decrease in the concentration of osteocalcin, a marker of bone formation, in the serum at 110 days of age

increased circulating cholesterol level ( J:66077 )

• in adult males

increased circulating HDL cholesterol level ( J:66077 )

• in adult males

insulin resistance ( J:66077 )

• in males at 4 months of age the insulin x free fatty acid product is increased suggesting the mice are insulin resistant

increased urine protein level ( J:88156 )

• in males and females at 1 year of age

abnormal response/metabolism to endogenous compounds ( J:82423 )

• 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

cardiovascular system

decreased heart weight ( J:62222 )

growth/size/body

ovarian follicular cyst ( J:16338 )

• hemorrhagic ovarian cysts

decreased body weight ( J:62222 )

• late pubertal and young adult body weight is decreased compared to controls

increased body weight ( J:114164 )

• in adult mice (over 44 days of age)

obese ( J:66077 )

• males at 4 months of age are obese

respiratory system

decreased lung weight ( J:62222 )

skeleton

skeleton phenotype ( J:114164 )

N	• unlike for the appendicular skeleton, no difference in the length of the axial skeleton is detected

decreased length of long bones ( J:114164 )

short ulna ( J:91765 )

• ulnae are 4% shorter and straighter than in wild-type mice

short femur ( J:62222 , J:114164 )

• in post-pubertal mice (J:62222)

• at 118 days of age but not at 31 or 65 days of age (J:114164)

short tibia ( J:114164 )

• at 118 days of age but not at 31 or 65 days of age

decreased bone mineral content ( J:62222 )

• bone mineral content normalized to body weight is decreased in the total body, femur and spine

decreased areal bone mineral density ( J:62222 )

• total areal bone mineral density is slightly decreased in adults

decreased bone mineral density of femur ( J:62222 )

• femur bone mineral density is decreased in adults

decreased compact bone area ( J:62222 )

• 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

decreased femoral compact bone area ( J:62222 )

increased compact bone area ( J:91765 )

• 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

decreased osteoblast cell number ( J:91765 )

• 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

decreased bone mineralization ( J:91765 )

• 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

decreased bone ossification ( J:91765 )

• 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

decreased bone strength ( J:62222 )

• decrease in maximal load

• however, other parameters, such as maximal stress and elastic modulus, are not significantly different from controls

embryo

abnormal mesonephros morphology ( J:108807 )

• 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

immune system

thymus hypoplasia ( J:110416 )

abnormal class switch recombination ( J:82423 )

• 17beta-estradiol-treated castrated mice fail to exhibit immunoglobulin switching unlike similarly treated wild-type mice

increased double-positive T cell number ( J:110416 )

• mice have increased double positive CD4+CD8+ thymocytes compared to in wild-type mice

abnormal B cell number ( J:82423 )

• 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

increased plasma cell number ( J:88156 )

• display plasmacytosis of the spleen and kidney

• lymph nodes also display an accumulation of plasma cells

decreased CD4-positive, alpha-beta T cell number ( J:110416 )

• mice have fewer single positive CD4+ and CD8+ thymocytes compared to in wild-type mice

decreased CD8-positive, alpha-beta T cell number ( J:110416 )

• mice have fewer single positive CD4+ and CD8+ thymocytes compared to in wild-type mice

increased spleen germinal center number ( J:88156 )

• despite being kept in a specific pathogen free environment mice spontaneously develop germinal centers

abnormal immunoglobulin level ( J:82423 )

• 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

increased IgG3 level ( J:88156 )

• in females

abnormal lymph node cell ratio ( J:88156 )

• display an accumulation of plasma cells

abnormal spleen physiology ( J:88156 )

• display plasmacytosis of the spleen

increased anti-double stranded DNA antibody level ( J:88156 )

• in males and females

glomerulonephritis ( J:88156 )

• seen in males and females by 1 year of age

renal/urinary system

increased urine protein level ( J:88156 )

• in males and females at 1 year of age

cortical renal glomerulopathies ( J:88156 )

• show some degree of mesangial sclerosis at 1 year of age

renal glomerular immunoglobulin deposits ( J:88156 )

• deposits of IgG are detected in the glomeruli

abnormal kidney physiology ( J:88156 )

• display plasmacytosis of the kidney

glomerulonephritis ( J:88156 )

• seen in males and females by 1 year of age

nervous system

abnormal hypothalamus morphology ( J:99716 )

• in the anteroventral periventricular nucleus the number of TH positive neurons is increased in males compared to wild-type males

abnormal innervation ( J:85911 )

• 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

adipose tissue

increased total body fat amount ( J:66077 )

• in males at 4 months of age but not at 1 or 2 months of age

increased gonadal fat pad weight ( J:66077 )

• in males at 4 months of age

increased retroperitoneal fat pad weight ( J:66077 )

• in males at 4 months of age

endocrine/exocrine glands

thymus hypoplasia ( J:110416 )

abnormal ovary morphology ( J:16338 )

• containing few granulosa cells

• hyperemic cystic ovaries

absent corpus luteum ( J:16338 )

ovarian follicular cyst ( J:16338 )

• hemorrhagic ovarian cysts

dilated rete testis ( J:36658 )

• 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

abnormal seminiferous tubule morphology ( J:36658 )

abnormal seminiferous tubule epithelium morphology ( J:36658 )

• at 20 days after birth, the seminiferous epithelium is thinner than normal

dilated seminiferous tubule ( J:36658 )

• 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

seminiferous tubule degeneration ( J:36658 )

• 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

decreased testis weight ( J:16338 , J:36658 )

(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)

limbs/digits/tail

short ulna ( J:91765 )

• ulnae are 4% shorter and straighter than in wild-type mice

decreased femoral compact bone area ( J:62222 )

short femur ( J:62222 , J:114164 )

• in post-pubertal mice (J:62222)

• at 118 days of age but not at 31 or 65 days of age (J:114164)

short tibia ( J:114164 )

• at 118 days of age but not at 31 or 65 days of age

hematopoietic system

thymus hypoplasia ( J:110416 )

abnormal class switch recombination ( J:82423 )

• 17beta-estradiol-treated castrated mice fail to exhibit immunoglobulin switching unlike similarly treated wild-type mice

increased double-positive T cell number ( J:110416 )

• mice have increased double positive CD4+CD8+ thymocytes compared to in wild-type mice

abnormal bone marrow cell number ( J:82423 )

• 17beta-estradiol-treated castrated mice fail to exhibit a decrease in bone marrow cellularity unlike similarly treated wild-type mice

abnormal B cell number ( J:82423 )

• 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

increased plasma cell number ( J:88156 )

• display plasmacytosis of the spleen and kidney

• lymph nodes also display an accumulation of plasma cells

decreased CD4-positive, alpha-beta T cell number ( J:110416 )

• mice have fewer single positive CD4+ and CD8+ thymocytes compared to in wild-type mice

decreased CD8-positive, alpha-beta T cell number ( J:110416 )

• mice have fewer single positive CD4+ and CD8+ thymocytes compared to in wild-type mice

increased spleen germinal center number ( J:88156 )

• despite being kept in a specific pathogen free environment mice spontaneously develop germinal centers

abnormal immunoglobulin level ( J:82423 )

• 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

increased IgG3 level ( J:88156 )

• in females

cellular

oligozoospermia ( J:16338 , J:36658 )

• 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)

teratozoospermia ( J:36658 )

• sperm with retroflexed bending in the midpiece region were commonly observed

• however, no major sperm head abnormalities were found to occur

detached sperm flagellum ( J:36658 )

• sperm heads were commonly detached from the flagellum

asthenozoospermia ( J:36658 )

• 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

Allelic Composition	Esr1^tm1Ksk/Esr1^tm1Ksk
Genetic Background	involves: 129P2/OlaHsd * C57BL/6N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Esr1^tm1Ksk mutation (2 available); any Esr1 mutation (68 available)

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

hematopoietic system

decreased thymus weight ( J:111590 )

• about a 50% reduction in thymus weight

decreased thymocyte number ( J:111590 )

abnormal thymus physiology ( J:111590 )

• estradiol induced thymic atrophy is reduced compared to wild-type controls and the subpopulation profile is not altered unlike in wild-type controls

abnormal definitive hematopoiesis ( J:63462 )

• following estradiol treatment hematopoietic progenitor subsets that are decreased in number in wild-type mice are not decreased in mutants

abnormal B cell differentiation ( J:63462 )

• unlike in wild-type mice, estradiol treatment does not change the numbers of immature or mature B cells

decreased immature B cell number ( J:63462 )

• decrease in the number of pre/pro and immature B cells

decreased B cell number ( J:63462 )

decreased mature B cell number ( J:63462 )

immune system

decreased thymus weight ( J:111590 )

• about a 50% reduction in thymus weight

decreased thymocyte number ( J:111590 )

abnormal thymus physiology ( J:111590 )

• estradiol induced thymic atrophy is reduced compared to wild-type controls and the subpopulation profile is not altered unlike in wild-type controls

abnormal B cell differentiation ( J:63462 )

• unlike in wild-type mice, estradiol treatment does not change the numbers of immature or mature B cells

decreased immature B cell number ( J:63462 )

• decrease in the number of pre/pro and immature B cells

decreased B cell number ( J:63462 )

decreased mature B cell number ( J:63462 )

endocrine/exocrine glands

decreased thymus weight ( J:111590 )

• about a 50% reduction in thymus weight

decreased thymocyte number ( J:111590 )

abnormal thymus physiology ( J:111590 )

• estradiol induced thymic atrophy is reduced compared to wild-type controls and the subpopulation profile is not altered unlike in wild-type controls

Allelic Composition	Esr1^tm1Ksk/Esr1^tm1Ksk
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Esr1^tm1Ksk mutation (2 available); any Esr1 mutation (68 available)

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

endocrine/exocrine glands

abnormal mammary gland development ( J:54215 )

• underdeveloped at 10 weeks of age with a rudimentary ductal network confined to the nipple region

integument

abnormal mammary gland development ( J:54215 )

• underdeveloped at 10 weeks of age with a rudimentary ductal network confined to the nipple region

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

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Esr1^tm1Ksk mutation (2 available); any Esr1 mutation (68 available)

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

reproductive system

abnormal testis morphology ( J:112350 )

• at 21 to 25 weeks of age in 4 males 5 of 8 testis were retracted up to near the bladder neck

• however, external examination did not reveal any defect in testicular descent

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

endocrine/exocrine glands

abnormal testis morphology ( J:112350 )

• at 21 to 25 weeks of age in 4 males 5 of 8 testis were retracted up to near the bladder neck

• however, external examination did not reveal any defect in testicular descent

Allelic Composition	Apoe^tm1Bres/Apoe^tm1Bres Esr1^tm1Ksk/Esr1^tm1Ksk
Genetic Background	B6.129P2-Apoe^tm1Bres Esr1^tm1Ksk

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Apoe^tm1Bres mutation (9 available); any Apoe mutation (156 available)
Esr1^tm1Ksk mutation (2 available); any Esr1 mutation (68 available)

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

cardiovascular system

atherosclerotic lesions ( J:68574 )

increased susceptibility to atherosclerosis ( J:68574 )

• in ovariectomized females the ability of treatment with estradiol to inhibit lesion progression is impaired

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:68574 )

N	• unlike ovariectomized wild-type for Esr1, xanthoma formation is rarely seen

abnormal circulating cholesterol level ( J:68574 )

• in ovariectomized females exogenous estradiol treatment fails to reduce fasting plasma cholesterol

reproductive system

uterus atrophy ( J:68574 )

• in ovariectomized females implanted with estradiol

Allelic Composition	Esr1^tm1Ksk/Esr1^tm1Ksk Esr2^tm1Unc/Esr2^tm1Unc
Genetic Background	involves: 129P2/OlaHsd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Esr1^tm1Ksk mutation (2 available); any Esr1 mutation (68 available)
Esr2^tm1Unc mutation (4 available); any Esr2 mutation (36 available)

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

reproductive system

oligozoospermia ( J:59105 )

• 80% reduction in epididymal sperm count relative to wild-type

asthenozoospermia ( J:59105 )

• 5% reduction in the motility of sperm obtained from the epididymis

abnormal ovary morphology ( J:59105 )

• postnatal transdifferentiation of portions of the ovary, resulting in structures resembling seminiferous tubules

• these tubule-like structures contained degenerating granulosa cells, sertoli-like cells, and in some cases, degenerating oocytes

absent corpus luteum ( J:59105 )

uterus hypoplasia ( J:59105 )

• evident at 2.5 to 7 months of age

• however, normal development of Mullerian-derived structures (uterus, cervix, and upper vagina) is seen

female infertility ( J:59105 )

male infertility ( J:59105 )

skeleton

long femur ( J:111108 )

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

abnormal vertebrae morphology ( J:111108 )

• at 18 months, vertebra height is increased compared to in to Esr1^tm1Ksk homozygotes

endocrine/exocrine glands

abnormal ovary morphology ( J:59105 )

• postnatal transdifferentiation of portions of the ovary, resulting in structures resembling seminiferous tubules

• these tubule-like structures contained degenerating granulosa cells, sertoli-like cells, and in some cases, degenerating oocytes

absent corpus luteum ( J:59105 )

homeostasis/metabolism

increased circulating luteinizing hormone level ( J:59105 )

• higher than those observed in Esr1^tm1Ksk homozygous mice

growth/size/body

increased body length ( J:111108 )

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

limbs/digits/tail

long femur ( J:111108 )

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

cellular

oligozoospermia ( J:59105 )

• 80% reduction in epididymal sperm count relative to wild-type

asthenozoospermia ( J:59105 )

• 5% reduction in the motility of sperm obtained from the epididymis

Allelic Composition	Esr1^tm1Ksk/Esr1^tm1Ksk Esr2^tm1Unc/Esr2^tm1Unc Inha^tm1Bay/Inha⁺
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac * 129S7/SvEvBrd

Find Mice

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

reproductive system

abnormal ovary morphology ( J:84989 )

• ovaries develop tubule-like structures unlike in wild-type mice

increased ovary tumor incidence ( J:84989 )

• in one mouse

neoplasm

increased ovary tumor incidence ( J:84989 )

• in one mouse

endocrine/exocrine glands

abnormal ovary morphology ( J:84989 )

• ovaries develop tubule-like structures unlike in wild-type mice

increased ovary tumor incidence ( J:84989 )

• in one mouse

Allelic Composition	Esr1^tm1Ksk/Esr1^tm1Ksk Inha^tm1Bay/Inha^tm1Bay
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac * 129S7/SvEvBrd

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Esr1^tm1Ksk mutation (2 available); any Esr1 mutation (68 available)
Inha^tm1Bay mutation (0 available); any Inha mutation (9 available)

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

mortality/aging

premature death ( J:84989 )

• male mice exhibit reduced survival compared with Esr1^tm1Ksk homozygotes that is similar to in Inha^tm1Bay homozygotes

• female mice exhibit reduced survival compared with Esr1^tm1Ksk or Inha^tm1Bay homozygotes

neoplasm

increased ovary tumor incidence ( J:84989 )

• tumors are larger than in Inha^tm1Bay homozygotes

• tumors contain tubule-like follicle-like structures

increased testis tumor incidence ( J:84989 )

• tumor cells contain diffuse granulosa-like cells

growth/size/body

decreased body weight ( J:84989 )

• in female mice compared with Esr1^tm1Ksk homozygotes, Inha^tm1Bay homozygotes, and wild-type mice

cachexia ( J:84989 )

• mice develop rapid cancer-associated wasting unlike wild-type mice that is more severe than in Inha^tm1Bay homozygotes

homeostasis/metabolism

increased circulating estradiol level ( J:84989 )

decreased circulating follicle stimulating hormone level ( J:84989 )

• in terminal mice compared with Inha^tm1Bay homozygotes

decreased circulating luteinizing hormone level ( J:84989 )

• in terminal mice compared with Inha^tm1Bay homozygotes

digestive/alimentary system

abnormal stomach mucosa morphology ( J:84989 )

• terminal mice exhibit mucosal atrophy in the stomach unlike in wild-type mice

abnormal stomach glandular epithelium morphology ( J:84989 )

• terminal mice exhibit depletion of parietal cells in the glandular stomach unlike in wild-type mice

immune system

liver inflammation ( J:84989 )

liver/biliary system

liver inflammation ( J:84989 )

abnormal hepatocyte morphology ( J:84989 )

• hepatocytes in terminal mice are darkened irregularly shaped and round surrounding the central vein unlike in wild-type mice

hepatic necrosis ( J:84989 )

• in terminal mice

skeleton

kyphoscoliosis ( J:84989 )

• in terminal mice

endocrine/exocrine glands

increased ovary tumor incidence ( J:84989 )

• tumors are larger than in Inha^tm1Bay homozygotes

• tumors contain tubule-like follicle-like structures

increased testis tumor incidence ( J:84989 )

• tumor cells contain diffuse granulosa-like cells

reproductive system

increased ovary tumor incidence ( J:84989 )

• tumors are larger than in Inha^tm1Bay homozygotes

• tumors contain tubule-like follicle-like structures

increased testis tumor incidence ( J:84989 )

• tumor cells contain diffuse granulosa-like cells

Allelic Composition	Esr1^tm1Ksk/Esr1^tm1Ksk Esr2^tm1Unc/Esr2^tm1Unc Inha^tm1Bay/Inha^tm1Bay
Genetic Background	involves: 129P2/OlaHsd * 129S6/SvEvTac * 129S7/SvEvBrd

Find Mice

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

mortality/aging

premature death ( J:84989 )

• most female mice die between 4 and 6 weeks of age and all die by 9 weeks of age

• male mice survival 19 weeks

reproductive system

decreased male germ cell number ( J:84989 )

• male germ cells are depleted and degenerated

abnormal ovary morphology ( J:84989 )

• tubule-like structures resembling Sertoli-like cells are found adjacent to tumor unlike in wild-type mice

increased ovary tumor incidence ( J:84989 )

• mice develop aggressive bilateral ovarian tumors with hemorrhagic foci

• tumors contain granulosa-like cells

abnormal seminiferous tubule morphology ( J:84989 )

• tubule lumens are filled with Sertoli cells unlike in wild-type mice

dilated seminiferous tubule ( J:84989 )

increased testis tumor incidence ( J:84989 )

• mice develop testicular tumors formed of granulosa-like cells with numerous sites of hemorrhage

• mice fail to develop early Sertoli cells unlike in Esr1^tm1Ksk Inha^tm1Bay or Esr2^tm1Unc Inha^tm1Bay double homozygotes

neoplasm

increased ovary tumor incidence ( J:84989 )

• mice develop aggressive bilateral ovarian tumors with hemorrhagic foci

• tumors contain granulosa-like cells

increased testis tumor incidence ( J:84989 )

• mice develop testicular tumors formed of granulosa-like cells with numerous sites of hemorrhage

• mice fail to develop early Sertoli cells unlike in Esr1^tm1Ksk Inha^tm1Bay or Esr2^tm1Unc Inha^tm1Bay double homozygotes

growth/size/body

decreased body weight ( J:84989 )

• compared with Esr1^tm1Ksk and Esr2^tm1Unc single homozygotes

cachexia ( J:84989 )

• at 26 weeks

increased body weight ( J:84989 )

• compared to in Inha^tm1Bay

homeostasis/metabolism

decreased circulating follicle stimulating hormone level ( J:84989 )

endocrine/exocrine glands

abnormal ovary morphology ( J:84989 )

• tubule-like structures resembling Sertoli-like cells are found adjacent to tumor unlike in wild-type mice

increased ovary tumor incidence ( J:84989 )

• mice develop aggressive bilateral ovarian tumors with hemorrhagic foci

• tumors contain granulosa-like cells

abnormal seminiferous tubule morphology ( J:84989 )

• tubule lumens are filled with Sertoli cells unlike in wild-type mice

dilated seminiferous tubule ( J:84989 )

increased testis tumor incidence ( J:84989 )

• mice develop testicular tumors formed of granulosa-like cells with numerous sites of hemorrhage

• mice fail to develop early Sertoli cells unlike in Esr1^tm1Ksk Inha^tm1Bay or Esr2^tm1Unc Inha^tm1Bay double homozygotes

cellular

decreased male germ cell number ( J:84989 )

• male germ cells are depleted and degenerated

Allelic Composition	Esr1^tm1Ksk/Esr1^tm1Ksk Esr2^tm1Unc/Esr2^tm1Unc
Genetic Background	involves: 129P2/OlaHsd * C57BL/6J

Find Mice

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

reproductive system

abnormal uterus weight ( J:115411 )

• 17beta-estradiol-induced increase in uterus weight is less than in similarly treated wild-type mice

decreased uterus weight ( J:115411 )

failure of ejaculation ( J:66582 )

• during a 30 min interaction with a receptive female males failed to show any ejaculations

behavior/neurological

decreased aggression towards male mice ( J:66582 )

• in a resident intruder assay aggressive behaviors toward the intruder male are greatly reduced and mice rarely show offensive attacks

• loss of offensive attacks is also seen when males are tested in a neutral cage

increased aggression towards female mice ( J:66582 )

• about 50% of males display defensive type aggression towards receptive females

abnormal copulation behavior ( J:66582 )

• during a 30 min interaction with a receptive female males failed to show any ultrasonic vocalizations, mounts, or intromissions; similar results are seen when the interaction is extended to 90 min

skeleton

short femur ( J:62222 )

• in post-pubertal mice

decreased bone mineral content ( J:62222 )

• bone mineral content normalized to body weight is decreased in the total body, femur and spine

decreased areal bone mineral density ( J:62222 )

• total areal bone mineral density is slightly decreased in adults

decreased bone mineral density of femur ( J:62222 )

• femur bone mineral density is decreased in adults

decreased compact bone area ( J:62222 )

decreased femoral compact bone area ( J:62222 )

homeostasis/metabolism

decreased circulating insulin-like growth factor I level ( J:62222 )

increased circulating leptin level ( J:66077 )

• in males at 4 months of age but not at 1 or 2 months of age

decreased circulating osteocalcin level ( J:62222 )

• decrease in the concentration of osteocalcin, a marker of bone formation, in the serum at 110 days of age

increased circulating cholesterol level ( J:66077 )

• in adult males

increased circulating HDL cholesterol level ( J:66077 )

• in adult males

insulin resistance ( J:66077 )

• in males at 4 months of age the insulin x free fatty acid product is increased suggesting the mice are insulin resistant

abnormal response/metabolism to endogenous compounds ( J:82423 , J:115411 )

	• 17beta-estradiol-induced increase in uterus weight is less than in similarly treated wild-type mice (J:115411) • treatment with 17beta-estradiol fails to inhibit vascular injury-induced increases in medial area unlike in similarly treated wild-type mice (J:115411) • however, vascular smooth muscle cell proliferation following injury and 17beta-estradiol treatment is normal (J:115411)
	• 17beta-estradiol-treated castrated mice fail to exhibit a decrease in bone marrow cellularity, a reduced decrease in the frequency of B cells, immunoglobulin switching, or an increase in production of immunoglobulins (IgA, IgG, and IgM) unlike similarly treated wild-type mice (J:82423)

growth/size/body

decreased body weight ( J:62222 )

• late pubertal and young adult body weight is decreased compared to controls

obese ( J:66077 )

• males at 4 months of age are obese

limbs/digits/tail

decreased femoral compact bone area ( J:62222 )

short femur ( J:62222 )

• in post-pubertal mice

immune system

thymus hypoplasia ( J:110416 )

abnormal class switch recombination ( J:82423 )

• 17beta-estradiol-treated castrated mice fail to exhibit immunoglobulin switching unlike similarly treated wild-type mice

increased double-positive T cell number ( J:110416 )

• mice have increased double positive CD4+CD8+ thymocytes compared to in wild-type mice

abnormal B cell number ( J:82423 )

• 17beta-estradiol-treated castrated mice fail to exhibit a reduced decrease in the frequency of B cells (including pre-B cells, pro-B cells, and newly formed B cells) compared with similarly treated wild-type mice

decreased CD4-positive, alpha-beta T cell number ( J:110416 )

• mice have fewer single positive CD4+ and CD8+ thymocytes compared to in wild-type mice

decreased CD8-positive, alpha-beta T cell number ( J:110416 )

• mice have fewer single positive CD4+ and CD8+ thymocytes compared to in wild-type mice

decreased spleen weight ( J:110416 )

abnormal immunoglobulin level ( J:82423 )

• 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

adipose tissue

increased total body fat amount ( J:66077 )

• in males at 4 months of age but not at 1 or 2 months of age

increased gonadal fat pad weight ( J:66077 )

• in males at 4 months of age

increased retroperitoneal fat pad weight ( J:66077 )

• in males at 4 months of age

hematopoietic system

thymus hypoplasia ( J:110416 )

abnormal class switch recombination ( J:82423 )

• 17beta-estradiol-treated castrated mice fail to exhibit immunoglobulin switching unlike similarly treated wild-type mice

increased double-positive T cell number ( J:110416 )

• mice have increased double positive CD4+CD8+ thymocytes compared to in wild-type mice

abnormal bone marrow cell number ( J:82423 )

• 17beta-estradiol-treated castrated mice fail to exhibit a decrease in bone marrow cellularity unlike similarly treated wild-type mice

abnormal B cell number ( J:82423 )

decreased CD4-positive, alpha-beta T cell number ( J:110416 )

• mice have fewer single positive CD4+ and CD8+ thymocytes compared to in wild-type mice

decreased CD8-positive, alpha-beta T cell number ( J:110416 )

• mice have fewer single positive CD4+ and CD8+ thymocytes compared to in wild-type mice

decreased spleen weight ( J:110416 )

abnormal immunoglobulin level ( J:82423 )

• 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

endocrine/exocrine glands

thymus hypoplasia ( J:110416 )

Allelic Composition	Esr1^tm1Ksk/Esr1^tm1Ksk Tg(MMTV-Erbb2)NK1Mul/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6J * FVB/N

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Esr1^tm1Ksk mutation (2 available); any Esr1 mutation (68 available)
Tg(MMTV-Erbb2)NK1Mul mutation (1 available)

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

neoplasm

increased mammary gland tumor incidence ( J:76653 )

increased tumor latency ( J:76653 )

• mice display 50% tumor incidence at 105 weeks of age compared to 52 weeks of age in transgenic mice wild-type for Esr1

• increasing progesterone levels accelerates tumor development

endocrine/exocrine glands

abnormal mammary gland development ( J:76653 )

• rudimentary mammary gland that fails to develop beyond the prepubertal stage

• however, duct structure is not different from homozygous null mice not carrying the transgene

increased mammary gland tumor incidence ( J:76653 )

integument

abnormal mammary gland development ( J:76653 )

• rudimentary mammary gland that fails to develop beyond the prepubertal stage

• however, duct structure is not different from homozygous null mice not carrying the transgene

increased mammary gland tumor incidence ( J:76653 )

Allelic Composition	Esr1^tm1Ksk/Esr1^tm1Ksk Tg(Wnt1)1Hev/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Esr1^tm1Ksk mutation (2 available); any Esr1 mutation (68 available)
Tg(Wnt1)1Hev mutation (2 available)

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

neoplasm

increased mammary adenocarcinoma incidence ( J:54215 )

• both sexes develop lobuloalveolar adenocarcinomas

increased tumor latency ( J:54215 )

• compared to transgenic mice wild-type for Esr1

endocrine/exocrine glands

abnormal mammary gland development ( J:54215 )

• virgin females display underdeveloped glands at 10 weeks of age with a hyperplastic rudimentary ductal network that lacks terminal end buds

mammary gland duct hyperplasia ( J:54215 )

• in the interior of the gland in virgin females

mammary gland alveolar hyperplasia ( J:54215 )

• in virgin females, regions of lobuloalveolar hyperplasia at the periphery of the gland

increased mammary adenocarcinoma incidence ( J:54215 )

• both sexes develop lobuloalveolar adenocarcinomas

mammary gland hyperplasia ( J:54215 )

• virgin females display underdeveloped glands at 10 weeks of age with a hyperplastic rudimentary ductal network that lacks terminal end buds

• unlike in transgenic mice wild-type for Esr1, hyperplasia does not progress with age in virgin females

• males display epithelial hyperplasia that does not extend into the inguinal fat pad similar to what is seen in females

integument

abnormal mammary gland development ( J:54215 )

• virgin females display underdeveloped glands at 10 weeks of age with a hyperplastic rudimentary ductal network that lacks terminal end buds

mammary gland duct hyperplasia ( J:54215 )

• in the interior of the gland in virgin females

mammary gland alveolar hyperplasia ( J:54215 )

• in virgin females, regions of lobuloalveolar hyperplasia at the periphery of the gland

increased mammary adenocarcinoma incidence ( J:54215 )

• both sexes develop lobuloalveolar adenocarcinomas

mammary gland hyperplasia ( J:54215 )

• virgin females display underdeveloped glands at 10 weeks of age with a hyperplastic rudimentary ductal network that lacks terminal end buds

• unlike in transgenic mice wild-type for Esr1, hyperplasia does not progress with age in virgin females

• males display epithelial hyperplasia that does not extend into the inguinal fat pad similar to what is seen in females

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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