Strain Name:
B6.129P2(Cg)-Esr1tm1.1Lja/Mmmh
Stock Number:
034289-MU
Citation ID:
RRID:MMRRC_034289-MU

Strain Information

Esr1tm1.1Lja
Name: estrogen receptor 1 (alpha); targeted mutation 1.1, J Larry Jameson
Synonyms: ERalphaAA, NERKI-, NERKI, ERalphaNERKI
Type: Allele
Species: Mus musculus (mouse)
Chromosome: 10
Alteration at locus: Knock-In
Esr1
Name: estrogen receptor 1 (alpha)
Synonyms: Estr, ERalpha, ER[a], ERa, Nr3a1, ER-alpha, ESR, Estra
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: 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
  • Estradiol/blood
  • Estrogen Receptor alpha/physiology
  • Estrus
  • Feedback, Physiological
  • Female
  • Gonadotropin-Releasing Hormone/pharmacology
  • Hypothalamo-Hypophyseal System/physiology
  • Luteinizing Hormone/blood
  • Mice
  • Mice, Inbred C57BL
  • Ovariectomy
  • Ovary/physiology
  • Response Elements/physiology
  • Signal Transduction/physiology
  • Estrogen Receptor alpha/genetics
  • Estrogens/pharmacology
  • Follicle Stimulating Hormone/blood
  • Follicle Stimulating Hormone/genetics
  • Follicle Stimulating Hormone/metabolism
  • Gene Expression Regulation/drug effects
  • Genotype
  • Gonadotropins/genetics
  • Luteinizing Hormone/genetics
  • Luteinizing Hormone/metabolism
  • Mice, Knockout
  • Models, Biological
  • Pituitary Gland/drug effects
  • Pituitary Gland/metabolism
  • Prolactin/genetics
  • Protein Subunits/genetics
  • Response Elements/drug effects
  • Electrophysiology
  • Estradiol/metabolism
  • Estradiol/pharmacology
  • Feedback, Physiological/drug effects
  • Feedback, Physiological/genetics
  • Gonadotropin-Releasing Hormone/metabolism
  • Male
  • Neurons/metabolism
  • Neurons/physiology
  • Pituitary Gland/physiology
  • Signal Transduction/drug effects
  • Signal Transduction/genetics
  • Synaptic Transmission/genetics
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 tht 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 C57BL/6 backround. We maintain this mutation congenic on 129/SvImJ and on C57BL/6 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, MD. PhD, Northwestern University
Primary Reference
  • Glidewell-Kenney C; Hurley LA; Pfaff L; Weiss J; Levine JE; Jameson JL, Nonclassical estrogen receptor alpha signaling mediates negative feedback in the female mouse reproductive axis., Proc Natl Acad Sci U S A 2007 May 8;104(19):8173-7. (Medline PMID: 17470805)
  • Glidewell-Kenney C; Weiss J; Hurley LA; Levine JE; Jameson JL, Estrogen receptor alpha signaling pathways differentially regulate gonadotropin subunit gene expression and serum follicle-stimulating hormone in the female mouse., Endocrinology 2008 Aug;149(8):4168-76. (Medline PMID: 18467444)
  • Christian CA; Glidewell-Kenney C; Jameson JL; Moenter SM, Classical estrogen receptor alpha signaling mediates negative and positive feedback on gonadotropin-releasing hormone neuron firing., Endocrinology 2008 Nov;149(11):5328-34. (Medline PMID: 18635656)

Colony and Husbandry Information

Females with mutation are infertile, although they can be superovulateded 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). We use a continuous breeding scheme with 1 male and 2 females /cage.

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
034289-MU-SPERM Cryo-preserved spermatozoa $437.00 / Non-Profit Aliquot Approximate quantity3
034289-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.