Strain Name:
129S1.129P2(Cg)-Esr1tm1.1Lja/Mmmh
Stock Number:
034288-MU
Citation ID:
RRID:MMRRC_034288-MU

Strain Information

Esr1tm1.1Lja
Name: estrogen receptor 1 (alpha); targeted mutation 1.1, J Larry Jameson
Synonyms: ERalphaNERKI, NERKI-, NERKI, ERalphaAA
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 10
Alteration at locus: Knock-In
Esr1
Name: estrogen receptor 1 (alpha)
Synonyms: ESR, ERalpha, ER[a], Nr3a1, ERa, Estr, Estra, ER-alpha
Type: Gene
Species: Mouse
Chromosome: 10
Alteration at locus: Knock-In
NCBI: 13982
HGNC: HGNC:3467
Homologene: 47906
Genetic Alterations
NERKI mice were generated by homologous recombination in HM-1 embryonic stem (ES) cells using dominantnegative selection. λ-Phage clones containing exon 3 of mERα were isolated from the λPIXII-129SvJ genomic library (Stratagene, La Jolla, CA). Exon 3 encodes the DNA binding domain of the first zinc finger. A targeting vector was constructed using approximately 10 kb of genomic sequence, a thymidine kinase cassette, and a neomycin cassette flanked by loxP sites. The E207A/G208A mutation was introduced into exon 3 by overlapping PCR (codons GAA GGC were changed to GCT GCA). The targeting construct contained a neomycin cassette flanked by lox P sites approximately 300 bp upstream of the mutated exon. The floxed neo cassette was removed by in vivo cre mediated recombination.
Genotype Determination
ES Cell Line
HM-1 derived from 129P2/OlaHsd-Hprtb-m3
Phenotype
Homozygous: Not characterized - heterozygous females are infertile.

Heterozygous: Heterozygous females display inhibited differentiation of mammary gland, decreased serum progesterone, enlarged uteri with cystic endometrial hyperplasia, increased luminal uterine epithelium height, and are anovulatory and infertile.There are consequences for both sexes in bone development, neuroendocrine reproductive axis, and in reproductive behavior due to the role that estrogen plays in these systems. Heterozygous males are fertile.
Mammalian Phenotype Terms
Allelic Composition: Esr1tm1.1Lja/Esr1+ (Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ )

Allelic Composition: Esr1tm1.1Lja/Esr1+ (Genetic Background: involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6 )

Allelic Composition: Esr1tm1.1Lja/Esr1tm1.1Mma (Genetic Background: involves: 129P2/OlaHsd * 129S2/SvPas * 129X1/SvJ * C57BL/6 )

MeSH Terms
  • Animals
  • Binding Sites
  • DNA/metabolism
  • Endometrial Hyperplasia/genetics
  • Endometrial Hyperplasia/pathology
  • Estrogen Receptor alpha
  • Female
  • Heterozygote
  • Hormones/pharmacology
  • Infertility, Female/genetics
  • Infertility, Female/physiopathology
  • Male
  • Mammary Glands, Animal/pathology
  • Mice
  • Mice, Mutant Strains
  • Mutation
  • Ovary/drug effects
  • Ovary/physiopathology
  • Ovulation/genetics
  • Ovulation Induction/methods
  • Progesterone/blood
  • Prolactin/metabolism
  • Receptors, Estrogen/genetics
  • Receptors, Estrogen/metabolism
  • Response Elements/genetics
  • Signal Transduction
  • Transcription Factor AP-1/genetics
  • Transcription Factor AP-1/metabolism
  • Uterus/abnormalities
  • Uterus/pathology
  • Zinc Fingers
  • Aquaporin 5/metabolism
  • Cell Line
  • Cell Proliferation
  • Cyclin D2
  • Cyclin-Dependent Kinase Inhibitor p21/metabolism
  • Cyclins/metabolism
  • Endometrium/cytology
  • Epithelial Cells/cytology
  • Estrogen Antagonists/metabolism
  • Estrogen Receptor alpha/genetics
  • Estrogen Receptor alpha/metabolism
  • Estrogens/metabolism
  • Genotype
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Organ Size
  • Protein Binding
  • Receptors, Progesterone/metabolism
  • Response Elements
  • Signal Transduction/physiology
  • Tamoxifen/analogs & derivatives
  • Tamoxifen/metabolism
  • Uterus/anatomy & histology
  • Bone Density/drug effects
  • Bone and Bones/drug effects
  • Bone and Bones/metabolism
  • Bone and Bones/physiology
  • Diaphyses/drug effects
  • Diaphyses/metabolism
  • Estradiol/blood
  • Estradiol/pharmacology
  • Estrogen Receptor alpha/physiology
  • Estrogens/pharmacology
  • Estrogens/physiology
  • Femur/drug effects
  • Femur/metabolism
  • Femur/physiology
  • Insulin-Like Growth Factor I/metabolism
  • Lumbar Vertebrae/drug effects
  • Lumbar Vertebrae/metabolism
  • Mice, Inbred Strains
  • Organ Size/drug effects
  • Ovariectomy
  • Phenotype
  • Random Allocation
  • Receptors, Estrogen/physiology
  • Signal Transduction/drug effects
  • Tibia/drug effects
  • Tibia/metabolism
  • Uterus/drug effects
Strain Development
Male chimeras were bred to WT 129/SvJ females to achieve germline transmission. Resulting progeny contained the neomycin cassette flanked by loxP sites. Heterozygous males were then bred to transgenic 129S1/SvImJ females expressing cre recombinase under the control of cytomegalovirus promoter. After the neomycin cassette was excised the CMV-cre transgene was bred out of the sucessive generations by selecting for animals with the mutation and without cre. The females with the mutation are infertile, so all breeding was done through het males and mated to 129S1/SvImJ females. In 2005, we began backcrossing males from the 129S1/SvImJ strain onto a C57B/L6 backround. We maintain this mutation congenic on 129/SvImJ and on C57B/L6 in two separate lines.
Suggested Control Mice

Wildtype littermates

MMRRC Genetic QC Summary
The MMRRC Centers have developed a genetic QC pipeline using MiniMUGA array genotyping to provide additional information on strain backgrounds for MMRRC congenic and inbred strains. For more information on when data may be available, or to request genotyping for a strain of interest, please contact mmrrc@missouri.edu. Older strains may not have this information.
  • Cancer
  • Cardiovascular
  • Endocrine Deficiency
  • Metabolism
  • Models for Human Disease
  • Neurobiology
  • Reproduction
Donor
J. Larry Jameson, M.D., Ph.D, Northwestern University
Primary Reference
  • Jakacka M, Ito M, Martinson F, Ishikawa T, Lee EJ, Jameson JL. An estrogen receptor (ER)alpha deoxyribonucleic acid-binding domain knock-in mutation provides evidence for nonclassical ER pathway signaling in vivo. Mol Endocrinol. 2002 Oct;16(10):2188-201 (Medline PMID: 12351685)
  • O'Brien JE, Peterson TJ, Tong MH, Lee EJ, Pfaff LE, Hewitt SC, Korach KS, Weiss J, Jameson JL. Estrogen-induced proliferation of uterine epithelial cells is independent of estrogen receptor alpha binding to classical estrogen response elements. J Biol Chem. 2006 Sep 8;281(36):26683-92. (Medline PMID: 16847062)
  • Syed FA; Modder UI; Fraser DG; Spelsberg TC; Rosen CJ; Krust A; Chambon P; Jameson JL; Khosla S, Skeletal effects of estrogen are mediated by opposing actions of classical and nonclassical estrogen receptor pathways., J Bone Miner Res 2005 Nov;20(11):1992-2001. (Medline PMID: 16234973)

Colony and Husbandry Information

Females with mutation are infertile, although they can be superoved to generate ooctyes for IVF or for natural mating with collection of 2-cell or blastocysts. The hormonal feedback does not appear to be sufficient to sustain a pregnancy in mutant females (het).

Colony Surveillance Program and Current Health Reports

Mice recovered from a cryo-archive will have health surveillance performed on recipient females. Health reports will be provided prior to shipment. If you require additional health status information, please email mmrrc@missouri.edu.

Order Request Information

Limited quantities of breeder mice (recovered litter) are available from a cryoarchive; recovered litter usually available to ship in 3 to 4 months.

Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.

Distribution of this strain requires submission of the MMRRC Conditions of Use (COU). A link to the COU web form will be provided via email after an order has been placed; the form should be completed then or the email forwarded to your institutional official for completion.

The donor or their institution limits the distribution to non-profit institutions only.

Additional charges may apply for any special requests. Shipping costs are in addition to the basic distribution/resuscitation fees. Information on shipping costs and any additional charges will be provided by the supplying MMRRC facility.

Click button to Request this one strain. (Use the MMRRC Catalog Search to request more than one strain.)
MMRRC Item # Description Distribution Fee / Unit (US $)
*Shipping & Handling not included*
Units Notes
034288-MU-RESUS Litter recovered from cryo-archive $2,624.00 / Non-Profit Litter Recovered litter4; additional fees for any special requests.
Cryopreserved material may be available upon request, please inquire to mmrrc@missouri.edu for more information.

1 The distribution fee covers the expense of rederiving mice from a live mouse; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

2 An aliquot contains a sufficient number of embryos (in one or more vials or straws and based on the transfer success rate of the MMRRC facility) to transfer into one to three recipients. The MMRRC makes no guarantee concerning embryo transfer success experienced in the recipient investigator's laboratory. Neither gender nor genotype ratios are guaranteed.

3 An aliquot is one straw or vial with sufficient sperm to recover at least one litter of mice, as per provided protocols, when performed at the MMRRC facility. The MMRRC makes no guarantee concerning the success of these procedures when performed outside the MMRRC facilities.

4 The distribution fee covers the expense of resuscitating mice from the cryo-archive; you will receive the resulting litter. The litter will contain at minimum one mutant carrier; the actual number of animals and the gender and genotype ratios will vary. (Typically, multiple breeder pairs can be established from the recovered litter.) Prior to shipment, the MMRRC will provide information about the animals recovered. If you anticipate or find that you need to request specific genotypes, genders or quantities of mice in excess of what is likely from a resuscitated litter, you may discuss available options and pricing with the supplying MMRRC facility.

To request material from the MMRRC: Please fill out our on-line request form (accessible from the catalog search results page, or click the Request this Strain button in the fees section). If you have questions or need assistance completing this form, you may call Customer Service at (800) 910-2291 (in USA or Canada) or (530) 757-5710 (international calls). Before you call, please have with you: the MMRRC item number, quantity needed, Bill-to and Ship-to contact information.