Overview

Also Known As:ERβ KO

Homozygous females for this knockout mutation are subfertile, producing fewer and smaller litters than wildtype controls. Decreased numbers of oocytes are also produced in response to superovulation compared to wildtype controls. Male homozygotes are fertile and exhibit epithelial hyperplasia in the bladder wall and prostatic collecting ducts. This mutant mouse strain may be useful in studies related to discerning the physiological roles of the estrogen signaling system.

Donating Investigator

Kenneth Korach, LRDT, NIEHS, NIH

Genetic overview

Genetic Background	Generation
	N8+N2F9 (2021-01-04 00:00:00)

Esr2^tm1Unc

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Esr2	estrogen receptor 2 (beta)

View Genetics

Research Applications

Internal/Organ Research
Endocrine Deficiency Research
Reproductive Biology Research

View All Research Applications

Base Price

Starting at:

$278.00 Domestic price for female 4-week

556.00 Domestic price for breeder pair

View Price List

Details

Detailed Description

Mice that are homozygous for this targeted allele are viable, normal in size and do not display any gross physical abnormalities. Stop codons inserted into exon 3 result in the production of truncated transcripts that are unlikely to be translated into a functional protein. Immunostaining of ovary tissue derived from homozygous females fails to detect protein product. Homozygous females are subfertile, producing fewer and smaller litters than wildtype controls. Decreased numbers of oocytes are also produced in response to superovulation (6 compared to 33.7 in wildtype controls). Male homozygotes are fertile and present no marked abnormalities other than epithelial hyperplasia in the bladder wall and prostatic collecting ducts. This mutant mouse strain may be useful in studies related to discerning the physiological roles of the estrogen signaling system.

Development

A targeting vector containing a neomycin resistance gene driven by the mouse phosphoglycerate kinase promoter was used to introduce stop codons into exon 3. The construct was introduced into 129P2/OlaHsd-derived E14TG2a embryonic stem (ES) cells (BK4 subline). Correctly targeted ES cells were injected into C57BL/6J blastocysts to obtain chimeric animals. These mice were then backcrossed to C57BL/6J for eight generations. In September 2001, the line was transferred to Taconic from the NIEHS and bred to C57BL/6NTac from which homozygotes were generated.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. While the 27 markers throughout the genome suggested a C57BL/6 genetic background, 2 of 5 markers that determine C57BL/6J from C57BL/6N were found to be segregating. These data suggest the mice sent to The Jackson Laboratory Repository were on a mixed C57BL/6J ; C57BL/6N genetic background.

Control Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Krege JH; Hodgin JB; Couse JF; Enmark E; Warner M; Mahler JF; Sar M; Korach KS; Gustafsson JA; Smithies O. 1998. Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci U S A 95(26):15677-82PubMed: 9861029 MGI: J:51663

View All References

Genetics

Esr2^tm1Unc

Allele Symbol: Esr2^tm1Unc

Allele Name	targeted mutation 1, University of North Carolina
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	BERKO; BERKOChapel Hill; betaERKO; beta-ERKO; Erb-; ERbeta-; ERbetaKO
Gene Symbol and Name	Esr2, estrogen receptor 2 (beta)
Gene Synonym(s)
Strain of Origin	129P2/OlaHsd
Chromosome	12
General Note	ES cell line = BK4, which is derived from a subclone of E14TG2a.
Molecular Note	A neomycin resistance cassette was inserted into exon 3 of the gene, introducing a stop codon and resulting in premature termination of translation of the Esr2 mRNA. Immunocytochemistry of ovary from homozygous mutant females showed no detectable Esr2 protein.
Mutations Made By	Kenneth Korach, LRDT, NIEHS, NIH

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Esr2^tm1Unc related

Internal/Organ Research
- Prostate
- Bladder
Endocrine Deficiency Research
- Gonad Defects
Reproductive Biology Research
- Endocrine Deficiencies Affecting Gonads
- Fertility Defects
  - females only

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Esr2^tm1Unc/Esr2^tm1Unc
involves: 129P2/OlaHsd

cellular phenotype

abnormal enterocyte apoptosis
- a few apoptotic cells are found in the colonic epithelium compared to in wild-type mice

abnormal enterocyte proliferation
- colonic cells exhibit a 1.6-fold higher than in wild-type mice

behavior/neurological phenotype

impaired contextual conditioning behavior
- during fear conditioning, mice exhibit an impairment in memory for context compared with wild-type mice

impaired cued conditioning behavior
- in male mice

abnormal behavior
- when suspended by their tails, fasted mice exhibit tremulousness, disturbed gait and balance, and spinning movement unlike similarly treated wild-type mice

digestive/alimentary phenotype

abnormal enterocyte proliferation
- colonic cells exhibit a 1.6-fold higher than in wild-type mice

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

colitis
- at 4 months, mice exhibit lymphoid infiltration below the epithelium in the colon unlike wild-type mice
- Normal - however, lymphoid infiltration at 12 months is less severe

abnormal enterocyte physiology
- colonic cells exhibit increased migration to the luminal surface compared with wild-type mice

abnormal enterocyte apoptosis
- a few apoptotic cells are found in the colonic epithelium compared to in wild-type mice

abnormal enterocyte morphology
- colonic epithelial cells exhibit reduced expression of differentiation markers compared to in wild-type mice
- colonic epithelium cells exhibit abnormal tight junctions and desmosomes compared to in wild-type mice

endocrine/exocrine gland phenotype

enlarged pancreatic islets
- mice exhibit a reduction in the percent of small islets and an increase in the percent of larger islets compared to in wild-type mice
- the average islet area is larger than in wild-type mice

decreased insulin secretion
- following glucose stimulation, peak insulin secretion is delayed compared to in similarly treated wild-type mice

abnormal mammary gland epithelium morphology
- at day 6 of lactation, mammary gland exhibits increased visible adipose tissue and reduced epithelium compared to in wild-type mice

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

abnormal mammary gland growth during pregnancy
- mid-pregnancy lobuloalveolar development is not as extensive as in wild-type mice

mammary gland alveolar hyperplasia
- on day 6 of lactation

abnormal mammary gland growth during lactation
- on day 6 of lactation, lobuloalveolar development only partially penetrates the fat pad and the alveoli are enlarged unlike in wild-type mice

growth/size/body region phenotype

cardiac hypertrophy
- after 8 months, mice exhibit ventricular hypertrophy compared with wild-type mice

enlarged heart
- after 8 months

increased body length
- at 4, but not 18, months

increased heart weight
- in sham-operated mice

increased body weight
- following induced myocardial infarction

cardiovascular system phenotype

abnormal intercalated disk morphology
- intercalating disks are more convoluted than in wild-type hearts with greater membrane lengths

abnormal myocardial fiber morphology
- after 8 months, the distance between myocytes is increased compared to in wild-type mice
- cardiomyocytes contain abnormal nuclear envelops
- myofibrils exhibit irregular orientation and heterogeneous length unlike in wild-type mice

increased vasodilation
- 17beta-estradiol-induced relaxation of aortic rings is more pronounced than in similarly treated wild-type rings

enlarged heart
- after 8 months

cardiac hypertrophy
- after 8 months, mice exhibit ventricular hypertrophy compared with wild-type mice

abnormal response to cardiac infarction
- following induced myocardial infarction, mice exhibit increased body weight and mortality, pleural effusions, and ascites compared with similarly treated wild-type mice
- Normal - however, infarct size is normal

enlarged myocardial fiber
- after 8 months, the diameter of myocytes is increased compared to in wild-type mice

increased heart weight
- in sham-operated mice

dilated heart ventricle
- after 8 months

hearing/vestibular/ear phenotype

abnormal auditory brainstem response
- following accoustic trauma, mice exhibit a greater shift in brainstem auditory evoked potential compared with similarly treated wild-type mice

homeostasis/metabolism phenotype

ascites
- following induced myocardial infarction

abnormal response to cardiac infarction
- Normal - however, infarct size is normal
- following induced myocardial infarction, mice exhibit increased body weight and mortality, pleural effusions, and ascites compared with similarly treated wild-type mice

abnormal response/metabolism to endogenous compounds
- 17beta-estradiol-induced relaxation of aortic rings is more pronounced than in similarly treated wild-type rings

decreased circulating glucose level
- in fasting mice prior to and after tamoxifen treatment

increased urine glycosaminoglycan level
- Normal - however, male mice have normal urine glycosaminoglycan content
- female mice exhibit an increase in urinary glycosaminoglycan content compared with wild-type mice

decreased insulin secretion
- following glucose stimulation, peak insulin secretion is delayed compared to in similarly treated wild-type mice

increased circulating glucose level
- in fed mice

increased insulin sensitivity

immune system phenotype

colitis
- at 4 months, mice exhibit lymphoid infiltration below the epithelium in the colon unlike wild-type mice
- Normal - however, lymphoid infiltration at 12 months is less severe

urinary bladder inflammation
- female mice exhibit an increase in T cell and macrophage infiltration in the female bladders unlike in wild-type mice

integument phenotype

mammary gland alveolar hyperplasia
- on day 6 of lactation

abnormal mammary gland growth during pregnancy
- mid-pregnancy lobuloalveolar development is not as extensive as in wild-type mice

abnormal mammary gland epithelium morphology
- at day 6 of lactation, mammary gland exhibits increased visible adipose tissue and reduced epithelium compared to in wild-type mice

abnormal mammary gland growth during lactation
- on day 6 of lactation, lobuloalveolar development only partially penetrates the fat pad and the alveoli are enlarged unlike in wild-type mice

limbs/digits/tail phenotype

long femur
- at 2 and 4, but not 18, months

mortality/aging

increased sensitivity to induced morbidity/mortality
- following induced myocardial infarction

muscle phenotype

abnormal myocardial fiber morphology
- cardiomyocytes contain abnormal nuclear envelops
- myofibrils exhibit irregular orientation and heterogeneous length unlike in wild-type mice
- after 8 months, the distance between myocytes is increased compared to in wild-type mice

increased vasodilation
- 17beta-estradiol-induced relaxation of aortic rings is more pronounced than in similarly treated wild-type rings

abnormal muscle contractility
- during fatiguing stimulation, male mice exhibit less of a decrease in force compared with similarly treated wild-type mice
- during recovery from fatiguing stimulation, male mice exhibit higher force generation than similarly treated wild-type mice

enlarged myocardial fiber
- after 8 months, the diameter of myocytes is increased compared to in wild-type mice

abnormal intercalated disk morphology
- intercalating disks are more convoluted than in wild-type hearts with greater membrane lengths

nervous system phenotype

abnormal excitatory postsynaptic potential
- female mice exhibit poorer fast synaptic transmission compared with wild-type mice

reduced long term potentiation
- in female mice

renal/urinary system phenotype

abnormal urinary bladder morphology
- Normal - however, bladders of male mice are normal
- at 8 months, female mice exhibit epithelial atrophy, massive ulceration of the bladder, and invasion of immune cells into the stroma and epithelium unlike in wild-type mice

increased urine glycosaminoglycan level
- female mice exhibit an increase in urinary glycosaminoglycan content compared with wild-type mice
- Normal - however, male mice have normal urine glycosaminoglycan content

abnormal urinary bladder urothelium morphology
- female mice exhibit ulceration and atrophy of bladder urothelium unlike in wild-type mice

urinary bladder inflammation
- female mice exhibit an increase in T cell and macrophage infiltration in the female bladders unlike in wild-type mice

abnormal urinary bladder physiology
- bladder permeability in female mice is higher than in wild-type mice

reproductive system phenotype

abnormal mammary gland growth during pregnancy
- mid-pregnancy lobuloalveolar development is not as extensive as in wild-type mice

respiratory system phenotype

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

abnormal surfactant physiology
- female mice exhibit an accumulation of surfactant inside the alveolar spaces unlike in wild-type mice

skeleton phenotype

long femur
- at 2 and 4, but not 18, months

abnormal long bone epiphyseal plate morphology
- the number of proliferative chondrocytes per column is increased while the number of hypertrophic chondrocytes per column is decreased compared to in wild-type mice

Genotype: Esr2^tm1Unc/Esr2^tm1Unc
involves: 129P2/OlaHsd * C57BL/6J

renal/urinary system phenotype

abnormal urinary bladder urothelium morphology
- at >3 months of age, male homozygotes exhibit epithelial hyperplasia in the bladder wall

reproductive system phenotype

decreased ovulation rate
- cles fail to fully respond and discharge their oocytes in response to hCG
- upon superovulation, immature (25-31 days) female homozygotes display an average yield of 6.0 ¿ 1.5 oocytes per female, whereas wild-type and heterozygous females yield 33.7 ¿ 4.8 and 52.5 ¿ 5.7 oocytes per female, respectively
- ovaries from superovulated immature female homozygotes display a large number of mature oocytes, indicating a normal response to pregnant mare serum gonadotropin, but contain less corpora lutea than stimulated wild-type ovaries, suggesting that some follicles fail to fully respond and discharge their oocytes in response to hCG

reduced female fertility
- female homozygotes show normal sexual behavior but produce significantly fewer litters than wild-type females (1.7 ¿ 1.0 vs 2.8 ¿ 0.4 litters/female, respectively)
- Normal - in contrast, young, sexually mature male homozygotes reproduce normally

anovulation
- upon superovulation, 2 of 11 immature (25-31 days) female homozygotes yield no detectable ova

abnormal cumulus oophorus morphology
- upon superovulation, immature (25-31 days) female homozygotes display a reduction in the cellular mass of the oocyte cumulus relative to wild-type and heterozygous littermates

prostate gland epithelial hyperplasia
- at >3 months of age, male homozygotes exhibit epithelial hyperplasia in the prostatic collecting ducts

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

decreased litter size
- female homozygotes show a significantly reduced litter size relative to wild-type females (3.1 ¿ 1.8 vs 8.8 ¿ 2.5 pups/litter, respectively)

impaired ovarian folliculogenesis
- at 7-9 weeks of age, young adult female homozygotes display ovaries with more early atretic follicles and fewer corpora lutea relative to wild-type mice, suggesting partial arrest of follicular development and less frequent follicular maturation

respiratory system phenotype

abnormal lung morphology
- lungs contain leukocyte, mainly granulocytes with some B lymphocytes, macrophages and eosinophils, infiltration unlike in wild-type mice

skeleton phenotype

increased compact bone area
- load-induced increase in cortical area is reduced 2-fold compared to in similarly treated wild-type mice

myelofibrosis
- at 2 years, mice develop myelofibrosis unlike wild-type mice

increased osteoblast cell number
- after 10 minutes of mechanical stress, the number of osteoblast-like cells is increased more than in similarly treated wild-type mice

abnormal bone mineralization
- load-induced increase in periosteal mineralization is decreased 50% compared to in similarly treated wild-type mice

cellular phenotype

abnormal cumulus oophorus morphology
- upon superovulation, immature (25-31 days) female homozygotes display a reduction in the cellular mass of the oocyte cumulus relative to wild-type and heterozygous littermates

increased keratinocyte apoptosis
- in hair matrix keratinocytes

endocrine/exocrine gland phenotype

impaired ovarian folliculogenesis
- at 7-9 weeks of age, young adult female homozygotes display ovaries with more early atretic follicles and fewer corpora lutea relative to wild-type mice, suggesting partial arrest of follicular development and less frequent follicular maturation

abnormal cumulus oophorus morphology
- upon superovulation, immature (25-31 days) female homozygotes display a reduction in the cellular mass of the oocyte cumulus relative to wild-type and heterozygous littermates

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

prostate gland epithelial hyperplasia
- at >3 months of age, male homozygotes exhibit epithelial hyperplasia in the prostatic collecting ducts

growth/size/body region phenotype

enlarged liver
- with leukocyte, mainly granulocytes with some B lymphocytes, infiltration

enlarged spleen
- profound by 1.5 years of age with leukocyte infiltration

spleen hyperplasia

hearing/vestibular/ear phenotype

abnormal cochlear IHC afferent innervation pattern
- at 2-6 months of age, female homozygotes exhibit some dilated afferent nerve endings on the cochlear IHCs, in the absence of a swollen stria vascularis
- Normal - however, middle and inner ear morphology is relatively normal relative to heterozygotes, and positive estrogen receptor alpha immunostaining is noted at the same locations as in control CBA/Ca mice

hematopoietic system phenotype

increased granulocyte number
- granulocyte populations in the bone marrow are increased 15% to 30% compared to in wild-type mice
- absolute numbers of granulocytes are increased 2-fold compared to in wild-type mice

increased neutrophil cell number
- in the blood at 1.5 years of age

increased pre-B cell number

increased pro-B cell number

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

abnormal leukopoiesis
- granulopoiesis is enhanced compared to in wild-type mice

enlarged spleen
- profound by 1.5 years of age with leukocyte infiltration

increased monocyte cell number
- in the blood at 1.5 years of age

spleen hypoplasia
- 17beta-estradiol-treated ovariectomized mice exhibit a reduction in spleen cellularity unlike similarly treated wild-type mice

abnormal lymphopoiesis
- at 1.5 years, some mice exhibit lymphoid blast crisis unlike in wild-type mice

increased erythrocyte cell number
- at 2 years, mice exhibit accumulation of red blood cells unlike in wild-type mice

increased leukocyte cell number
- at 1.5 years, leukocyte numbers in the blood is increased 3- to 4-fold compared to in wild-type mice

spleen hyperplasia

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

anemia
- at 2 years in surviving mice

increased bone marrow cell number
- as early as 1 month of age

increased megakaryocyte cell number
- in the spleen and bone marrow

homeostasis/metabolism phenotype

abnormal response/metabolism to endogenous compounds
- 17beta-estradiol-treated castrated mice fail to exhibit a decrease in bone marrow cellularity and exhibit a reduced decrease in the frequency of B cells unlike similarly treated wild-type mice
- Normal - however, 17beta-estradiol-treated castrated mice exhibit immunoglobulin switching and increased immunoglobulin levels
- 17beta-estradiol-treated ovariectomized mice fail to exhibit a reduction in the cortex area ration of the thymus, alterations in thymocyte frequencies, or reduced IGF-1 serum levels unlike similarly treated wild-type mice
- 17beta-estradiol-treated ovariectomized mice exhibit a reduction in spleen cellularity unlike similarly treated wild-type mice
- Normal - however, 17beta-estradiol-treated ovariectomized mice exhibit normal reduction in thymus weight and cellularity

increased circulating insulin-like growth factor I level
- 17beta-estradiol-treated ovariectomized mice fail to exhibit a reduction in IGF-1 serum levels unlike similarly treated wild-type mice

behavior/neurological phenotype

increased aggression towards males
- in a resident intruder assay aggressive behaviors toward the intruder male are increased in the first trial but not in subsequent trials compared to wild-type controls
- younger mice and naive (not used in sexual behavior assays) mice display increased aggression compared to wild-type controls

abnormal spatial learning
- ovariectomized mice exhibit slower escape time from a Morris water maze compared with similarly treated wild-type mice
- Normal - however, ovariectomized mice treated with 17beta-estradiol exhibit normal escape from a cued water maze
- ovariectomized mice treated with 17beta-estradiol exhibit reduced escape platform learning in a Morris water maze compared with similarly treated wild-type mice

abnormal sexual interaction
- in a 90 min test with a receptive female the number of mounts is decreased; however, the ratio of mounts and intromissions to ejaculations is reduced indicating increased sexual excitement

immune system phenotype

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

enlarged spleen
- profound by 1.5 years of age with leukocyte infiltration

increased leukocyte cell number
- at 1.5 years, leukocyte numbers in the blood is increased 3- to 4-fold compared to in wild-type mice

increased pre-B cell number

increased granulocyte number
- granulocyte populations in the bone marrow are increased 15% to 30% compared to in wild-type mice
- absolute numbers of granulocytes are increased 2-fold compared to in wild-type mice

increased neutrophil cell number
- in the blood at 1.5 years of age

spleen hyperplasia

increased pro-B cell number

abnormal leukopoiesis
- granulopoiesis is enhanced compared to in wild-type mice

abnormal lymphopoiesis
- at 1.5 years, some mice exhibit lymphoid blast crisis unlike in wild-type mice

enlarged lymph nodes
- by 1.5 years of age

increased monocyte cell number
- in the blood at 1.5 years of age

spleen hypoplasia
- 17beta-estradiol-treated ovariectomized mice exhibit a reduction in spleen cellularity unlike similarly treated wild-type mice

cardiovascular system phenotype

abnormal vascular smooth muscle morphology
- vascular smooth muscle cells are half normal size

increased systemic arterial blood pressure
- increased blood pressure in most mice at 6-7 months of age
- blood pressure remains elevated to 22 months of age
- heart rate unchanged

abnormal vascular smooth muscle physiology
- absence of voltage dependent outward current

increased vasoconstriction

integument phenotype

increased keratinocyte apoptosis
- in hair matrix keratinocytes

accelerated hair follicle regression
- apoptosis of hair follicle and hair matrix keratinocyte is increased compared to in wild-type mice confirming accelerated apoptosis-driven hair follicle regression

thin epidermis
- dermal thickness is less than in wild-type mice

abnormal hair cycle catagen phase
- at P17 and P19, more hair follicles are in catagen than in wild-type mice

liver/biliary system phenotype

enlarged liver
- with leukocyte, mainly granulocytes with some B lymphocytes, infiltration

mammalian phenotype

reproductive system phenotype
- Normal - at 7-9 weeks of age, female homozygotes display normal mammary gland histology and appear to lactate efficiently, as judged by normal nursing behavior and growth of their pups

behavior/neurological phenotype
- Normal - unlike mice null for Esr1, no defect in retention is detected in an inhibitory avoidance behavior assay

skeleton phenotype
- Normal - unlike in Esr1 null mice, no defects are detected in the skeletal system

muscle phenotype

abnormal vascular smooth muscle physiology
- absence of voltage dependent outward current

abnormal vascular smooth muscle morphology
- vascular smooth muscle cells are half normal size

abnormal muscle electrophysiology
- absence of voltage dependent outward current in vascular smooth muscle cells

increased vasoconstriction

neoplasm

increased chronic myelocytic leukemia incidence
- mice exhibit a myeloproliferative disease with granulocytosis and massive blast cell infiltration of hematopoietic and nonhematopoietic organs

nervous system phenotype

abnormal substantia nigra morphology
- by 2 yrs of age, homozygotes exhibit severe degeneration of neuronal cell bodies in the substantia nigra

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

abnormal astrocyte morphology
- at 1 year of age, both male and female homozygotes show a mild to moderate increase in the number of astrocytes relative to wild-type counterparts; however, no significant differences in the number or morphology of GFAP immunoreactive cells are observed at 2 years of age
- at 2 months of age, an increase in the number of hypertrophic astrocytes is also observed in the white matter adjacent to regions of neuronal loss
- at 2 months of age, male homozygotes display hypertrophic astroglial cells, with swollen cell bodies and thicker processes relative to wild-type mice
- t 2 years of age

abnormal neocortex morphology
- at 2 months of age, homozygotes display hypocellularity of the neocortex, with severe neuronal deficit in layers II, III, IV and V, extending from the somatosensory region to the parietal region

decreased neuron number
- at 2 years of age, homozygotes show a decreased number of small neurons in layers II, III, IV, and V of the somatosensory cortex, as well as loss of large pyramidal neurons in layer V
- rsal raphe nucleus, locus coeruleus, solitary tract nucleus, medial preoptic area, and medial amygdala nucleus
- at 1 year of age, both male and female homozygotes exhibit neuronal hypocellularity in the same brain regions, but the overall brain size is still similar to that of wild-type counterparts
- at 2 months of age, homozygotes display a severe neuronal deficit in layers II, III, IV and V of the neocortex, as well as significant neuronal loss in the basal forebrain, hypothalamus, amygdala, ventral tegmental area, substantia nigra, central gray, dorsal raphe nucleus, locus coeruleus, solitary tract nucleus, medial preoptic area, and medial amygdala nucleus
- at 2 months of age, neuronal loss is much more pronounced in male than in female homozygotes
- Normal - no obvious neuronal deficit is found in the paraventricular nucleus of hypothalamus (PVN), hippocampus, caudate-putamen, thalamus, or cerebellum at 2 months of age or later

abnormal somatosensory cortex morphology
- at 2 months of age, homozygotes display a significant reduction in the number of neurons in layer II, III, IV, and V of the somatosensory cortex
- by 2 years of age, an obvious atrophy affecting all layers is noted in the somatosensory-parietal cortex; however, thinning of layers IV and V is particularly pronounced

astrocytosis
- only a mild increase of GFAP immunoreactivity is detected in the hippocampus and cerebellum
- Normal - strikingly, no astrogliosis is observed in regions of the somatosensory cortex with severe neuronal loss
- at 2 months of age, male homozygotes show an increased number of GFAP-immunoreactive cells throughout many brain areas, esp. in the basal forebrain, hypothalamus, and amygdala; females are less affected than males

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

abnormal cochlear IHC afferent innervation pattern
- at 2-6 months of age, female homozygotes exhibit some dilated afferent nerve endings on the cochlear IHCs, in the absence of a swollen stria vascularis
- Normal - however, middle and inner ear morphology is relatively normal relative to heterozygotes, and positive estrogen receptor alpha immunostaining is noted at the same locations as in control CBA/Ca mice

Genotype: Esr2^tm1Unc/Esr2^tm1Unc
involves: 129P2/OlaHsd * C57BL/6

cardiovascular system phenotype

abnormal response of heart to induced stress
- female mice treated with isoproterenol prior to ischemia, exhibit less recovery of postischemic function compared with similarly treated wild-type mice

homeostasis/metabolism phenotype

increased circulating luteinizing hormone level
- higher than normal luteinizing hormone levels are further elevated by ovariectomy

decreased physiological sensitivity to xenobiotic
- female mice treated with isoproterenol prior to ischemia, exhibit less recovery of postischemic function, phosphocreatine, and ATP compared with similarly treated wild-type mice

abnormal response of heart to induced stress
- female mice treated with isoproterenol prior to ischemia, exhibit less recovery of postischemic function compared with similarly treated wild-type mice

The following phenotype relates to a compound genotype created using this strain

Genotype: Esr2^tm1Unc/Esr2^tm1Unc
B6.129P2-Esr2

integument phenotype

hyporesponsive to tactile stimuli
- female mice exhibit an increased threshold to mechanical nociception compared with similarly treated wild-type female mice
- Normal - however, male mice exhibit normal mechanical nociception

abnormal nociception after inflammation
- Normal - however, male mice exhibit normal mechanical nociception after inflammation
- female mice exhibit an increased threshold to mechanical nociception following inflammation compared with similarly treated wild-type female mice

nervous system phenotype

decreased serotonin level
- serotonin levels are decreased in the stria terminalis, preoptic area, and hippocampus compared to in wild-type mice

behavior/neurological phenotype

hyporesponsive to tactile stimuli
- Normal - however, male mice exhibit normal mechanical nociception
- female mice exhibit an increased threshold to mechanical nociception compared with similarly treated wild-type female mice

increased anxiety-related response
- in an elevated plus maze, mice spend less time exploring the open arms compared with wild-type mice

abnormal nociception after inflammation
- Normal - however, male mice exhibit normal mechanical nociception after inflammation
- female mice exhibit an increased threshold to mechanical nociception following inflammation compared with similarly treated wild-type female mice

decreased exploration in new environment
- in an elevated plus maze, mice spend less time exploring the open arms compared with wild-type mice

homeostasis/metabolism phenotype

decreased serotonin level
- serotonin levels are decreased in the stria terminalis, preoptic area, and hippocampus compared to in wild-type mice

decreased dopamine level
- in the caudate putamen

References

Krege JH; Hodgin JB; Couse JF; Enmark E; Warner M; Mahler JF; Sar M; Korach KS; Gustafsson JA; Smithies O. 1998. Generation and reproductive phenotypes of mice lacking estrogen receptor beta. Proc Natl Acad Sci U S A 95(26):15677-82PubMed: 9861029 MGI: J:51663

Additional - Esr2^tm1Unc related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Esr2
- Standard PCR:Esr2
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

The line is maintained by breeding heterozygous females to homozygous males.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Homozygote
Citation
When using the ERβ KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #004745 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Breeder Pair

Sex

Genotype

Price

Female
Male

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous for Esr2<tm1Unc>

Related Products and Services

Frozen Mouse Embryo	B6.129P2-Esr2<tm1Unc>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129P2-Esr2<tm1Unc>/J Frozen Embryos	$2595.00
Frozen Mouse Embryo	B6.129P2-Esr2<tm1Unc>/J Frozen Embryos	$3373.50
Frozen Mouse Embryo	B6.129P2-Esr2<tm1Unc>/J Frozen Embryos	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:ERβ KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Esr2tm1Unc

Allele Symbol: Esr2tm1Unc

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Esr2tm1Unc related

Mammalian Phenotype Terms by Genotype

Genotype: Esr2tm1Unc/Esr2tm1Uncinvolves: 129P2/OlaHsd

cellular phenotype

behavior/neurological phenotype

digestive/alimentary phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

cardiovascular system phenotype

hearing/vestibular/ear phenotype

homeostasis/metabolism phenotype

immune system phenotype

integument phenotype

limbs/digits/tail phenotype

mortality/aging

muscle phenotype

nervous system phenotype

renal/urinary system phenotype

reproductive system phenotype

respiratory system phenotype

skeleton phenotype

Genotype: Esr2tm1Unc/Esr2tm1Uncinvolves: 129P2/OlaHsd * C57BL/6J

renal/urinary system phenotype

reproductive system phenotype

respiratory system phenotype

skeleton phenotype

cellular phenotype

endocrine/exocrine gland phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

behavior/neurological phenotype

immune system phenotype

cardiovascular system phenotype

integument phenotype

liver/biliary system phenotype

mammalian phenotype

muscle phenotype

neoplasm

nervous system phenotype

Genotype: Esr2tm1Unc/Esr2tm1Uncinvolves: 129P2/OlaHsd * C57BL/6

cardiovascular system phenotype

homeostasis/metabolism phenotype

Genotype: Esr2tm1Unc/Esr2tm1UncB6.129P2-Esr2

integument phenotype

nervous system phenotype

behavior/neurological phenotype

homeostasis/metabolism phenotype

References

Additional - Esr2tm1Unc related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Esr2^tm1Unc

Allele Symbol: Esr2^tm1Unc

Genotype: Esr2^tm1Unc related

Genotype: Esr2^tm1Unc/Esr2^tm1Unc
involves: 129P2/OlaHsd

Genotype: Esr2^tm1Unc/Esr2^tm1Unc
involves: 129P2/OlaHsd * C57BL/6J

Genotype: Esr2^tm1Unc/Esr2^tm1Unc
involves: 129P2/OlaHsd * C57BL/6

Genotype: Esr2^tm1Unc/Esr2^tm1Unc
B6.129P2-Esr2

Additional - Esr2^tm1Unc related