RediMODEL transgenics in C. elegans

ESR1 - estrogen receptor 1 (alpha)

GENE DESCRIPTION:

  • Function: ESR1 is ligand-activated transcription factor needed for sexual development and reproductive function.
  • Disease: Genetic defects in ESR1 have been found to be highly associated with Mammary Neoplasms.
 

Products:

RediMODEL Kits -  a series of humanized animal models specifically engineered for easy measurement of phenotype defects caused by clinically-relevant disease mutations.   

rediMODEL-KO

ESR1 RediMODEL KO: Generated in the C. elegans homolog daf-12 as partial deletion allele leading to the removal of the ligand binding domain in the coding sequence. The daf-12 deletion knock-out (KO) results in loss of function in ESR1. Major phenotype readout for KO line is loss of SDS resistance in a dauer induction assay. An all-coding deletion mutant is currently available as gene-knock out.

 

ESR1 RediMODEL KI: Generated in the C. elegans homolog daf-12 with partial gene replacement to create ESR1 knock-in (KI) strain. Entire coding of ligand binding domain of daf-12 is replaced with wild-type ESR1 ligand binding domain sequence. A ESR1 gene replacement is currently available as a humanized wt line.

 

ESR1 RediMODEL CV: Generated in the C. elegans homolog daf-12 with partial gene replacement to create ESR1 knock-in (CV) strain. Entire coding of ligand binding domain of daf-12 is replaced with wild-type ESR1 ligand binding domain sequence containing amino-acid change polymophism that has been observed in patient populations. Upon request, a ESR1 line with client-specific polymorphism is made as a clinical variant allele.

 

RediMODEL knock out in C. elegans | $845 each kit Buy Now

ESR1 - estrogen receptor 1 (alpha)

DESCRIPTION:

ESR1 is ligand-activated transcription factor (nuclear hormone receptor) needed for sexual development and reproductive function. (other names: ER, ESR, Era, ESRA, ESTRR, NR3A1)

DISEASES:

Mammary Neoplasms, Myocardial Infarction, Estrogen Resistance, Malignant neoplasm of breast, Obesity, Prostatic Intraepithelial Neoplasias, Alzheimer's Disease, Coronary Artery Disease, Neoplasm Metastasis, Fibroid Tumor, Endometrial Neoplasms, Osteoporosis, Migraine Disorders, Prostatic Neoplasms, Male infertility, Liver carcinoma, Atherosclerosis, Animal Mammary Neoplasms, Adenocarcinoma, Female Infertility, Oligospermia, leukemia, Lung Neoplasms, Liver neoplasms, Familal Breast Cancer, Astrocytoma, Neoplastic Cell Transformation, Sudden Cardiac Arrest, Neoplasm Recurrence, Glomerulonephritis, Metabolic Bone Disorder, Feminization, Substance-Induced Psychoses, Peripheral Neuropathy, Mesothelioma, Bladder Neoplasm, Female Urogenital Diseases.*

* All disease associations scored above a 0.1 threshold from disgenet.com

Protein domain - slc6a3 dat-1.png

HOMOLOGY (subdomain)

Human Gene ESR1 Alignment         
C. elegans Gene daf-12 align
Identity 23%
Similarity 44%

KNOCK-OUT of C. elegans gene:

daf-12: has homologous function similar to ESR1. The daf-12 gene functions as a nuclear hormone receptor. When daf-12 is expressed and active, it controls entry into a delayed development life-state (dauer). Deletion mutations in daf-12  ligand binding domain cause commitment to the  dauer constitutive loss-of-function phenotype. The canonical allele in daf-12 is (rh273), which contains a LBD domain defect of R564H and is thought to render the gene non-activatable by native ligand. The most easily measured phenotype for the loss of ligand binding function is decreased pumping from constitutive dauer formation. To decrease the risk of background mutations, this LBD-disrupted strain is 4x outcrossed. The resulting outcrossed strain containing (rh273) allele is offered as the ESR1 RediMODEL-KO strain. The KO strain is confirmed by PCR and shipped in the RediMODEL kit format. Included in kit is N2 wild type strain as reference control.


RediMODEL Kit Details:

Each kit arrives with 3 frozen tubes of ESR1 RediMODEL-KO and 3 tubes of N2 for control and all materials needed for 2+ days of growth.

PLEASE PUT FROZEN TUBES AT -80C UPON ARRIVAL.

Authentication:

Genotype and phenotype data provides a capacity for researcher to monitor and retain authentication, as per NIH guidelines.

Genotype data:

PCR Assay

The RediMODEL-KO line is verified and followed by PCR. The gel image in Genotype Data shows the expected PCR band pattern in an agarose gel for the primer set supplied with the RediMODEL kit.



amplicon size
wild type 500 bp
ESR1 RediMODEL-KO 900 bp
 

Phenotype data:

Bio Assay

The RediMODEL-KO line's activity is best followed by monitoring changes in neurotransmission rates of the food intake. Pharynx pumping increases and decreases are easily monitored in ScreenChip system assay (Nemametrix.com). using the Low Stimulation Pharynx Pumping Protocol (P001), a significant difference in pumping rate is observed.

Low Stimulation Pharynx Pumping Protocol (P001)


strain wt frequency (Hz)
N2 wild type 100%
ESR1 RediMODEL-KO 10%

Discover ESR1 RediMODEL-KO Kit: | $845 each kit Buy Now

Discover RediMODEL-KO Kit: | $845 each kit

Inquire on ESR1 RediMODEL-KO

Please provide contact info and a company representative will contact you soon with preorder invoicing details.

ESR1 rediMODEL-KO inquiry

RediMODEL knock in of human gene replacement in C. elegans | $845 each kit Buy Now

ESR1 - estrogen receptor 1 (alpha)

DESCRIPTION:

ESR1 is ligand activated transcription factor needed for sexual development and reproductive function. (other names: ER, ESR, Era, ESRA, ESTRR, NR3A1)

DISEASES:

Mammary Neoplasms, Myocardial Infarction, Estrogen Resistance, Malignant neoplasm of breast, Obesity, Prostatic Intraepithelial Neoplasias, Alzheimer's Disease, Coronary Artery Disease, Neoplasm Metastasis, Fibroid Tumor, Endometrial Neoplasms, Osteoporosis, Migraine Disorders, Prostatic Neoplasms, Male infertility, Liver carcinoma, Atherosclerosis, Animal Mammary Neoplasms, Adenocarcinoma, Female Infertility, Oligospermia, leukemia, Lung Neoplasms, Liver neoplasms, Familal Breast Cancer, Astrocytoma, Neoplastic Cell Transformation, Sudden Cardiac Arrest, Neoplasm Recurrence, Glomerulonephritis, Metabolic Bone Disorder, Feminization, Substance-Induced Psychoses, Peripheral Neuropathy, Mesothelioma, Bladder Neoplasm, Female Urogenital Diseases.*

* All disease associations scored above a 0.1 threshold from disgenet.com

Protein domain - slc6a3 dat-1.png

HOMOLOGY (subdomain)

Human Gene ESR1 Alignment         
C. elegans Gene daf-12 align
Identity 23%
Similarity 44%
RediMODEL-KI logo sml.png

HUMANIZED C. elegans:

daf-12: has homologous function similar to ESR1. The daf-12 gene functions as a nuclear hormone receptor. When daf-12 is expressed and active, it controls entry into a delayed development life-state (dauer). Deletion mutations in daf-12  ligand binding domain cause commitment to the  dauer constitutive loss-of-function phenotype. A daf-12 allele (rh273) containing  a LBD domain defect of R564H is used as ESR1 RediMODEL KO strain.  To create a humanized worm, ESR1 ligand binding domain (LBD) is swapped for the daf-12 LBD.   Installation of ESR1 LBD in replacement of daf-12 LBD causes restoration of normal pumping phenotype and is offered as ESR1 RediMODEL-KI control strain. The KI strain is confirmed by PCR and shipped in the RediMODEL kit format. Included in kit is ESR1 RediMODEL-KO as reference control.


RediMODEL Kit Details:

Each kit arrives with 3 frozen tubes of ESR1 RediMODEL-KI and 3 tubes of N2 for control and all materials needed for 2+ days of growth.

PLEASE PUT FROZEN TUBES AT -80C UPON ARRIVAL.

Authentication:

Genotype and phenotype data provides a capacity for researcher to monitor and retain authentication, as per NIH guidelines.

Genotype data:

PCR Assay

The RediMODEL-KI line is verified and followed by PCR. The gel image in Genotype Data shows the expected PCR band pattern in an agarose gel for the primer set supplied with the RediMODEL kit.

amplicon size
wild type 500 bp
ESR1 RediMODEL-KI 900 bp
 

Phenotype data:

Bio Assay

The RediMODEL-KI line's activity is best followed by monitoring changes in neurotransmission rates of the food intake. Pharynx pumping increases and decreases are easily monitored in ScreenChip system assay (Nemametrix.com). using the Low Stimulation Pharynx Pumping Protocol (P001), a significant difference in pumping rate is observed.

Low Stimulation Pharynx Pumping Protocol (P001)

strain wt frequency (Hz)
ESR1 RediMODEL-KO 10%
ESR1 RediMODEL-KI 100%

Discover ESR1 RediMODEL-KI Kit: | $845 each kit Buy Now

RediMODEL knock out in C. elegans | $6695 each kit Buy Now

ESR1 - estrogen receptor 1 (alpha)

DESCRIPTION:

ESR1 is ligand activated transcription factor needed for sexual development and reproductive function. (other names: ER, ESR, Era, ESRA, ESTRR, NR3A1)

DISEASES:

Mammary Neoplasms, Myocardial Infarction, Estrogen Resistance, Malignant neoplasm of breast, Obesity, Prostatic Intraepithelial Neoplasias, Alzheimer's Disease, Coronary Artery Disease, Neoplasm Metastasis, Fibroid Tumor, Endometrial Neoplasms, Osteoporosis, Migraine Disorders, Prostatic Neoplasms, Male infertility, Liver carcinoma, Atherosclerosis, Animal Mammary Neoplasms, Adenocarcinoma, Female Infertility, Oligospermia, leukemia, Lung Neoplasms, Liver neoplasms, Familal Breast Cancer, Astrocytoma, Neoplastic Cell Transformation, Sudden Cardiac Arrest, Neoplasm Recurrence, Glomerulonephritis, Metabolic Bone Disorder, Feminization, Substance-Induced Psychoses, Peripheral Neuropathy, Mesothelioma, Bladder Neoplasm, Female Urogenital Diseases.*

* All disease associations scored above a 0.1 threshold from disgenet.com

Protein domain - slc6a3 dat-1.png

HOMOLOGY (subdomain)

Human Gene ESR1 Alignment         
C. elegans Gene daf-12 align
Identity 23%
Similarity 44%
rediMODEL-KO

CLINICAL VARIANT C. elegans:

daf-12: has homologous function similar to ESR1. The daf-12 gene functions as a nuclear hormone receptor. When daf-12 is expressed and active, it controls entry into a delayed development life-state (dauer). Deletion mutations in daf-12  ligand binding domain cause commitment to the  dauer constitutive loss-of-function phenotype. A daf-12 allele (rh273) containing  a LBD domain defect of R564H is used as ESR1 RediMODEL KO strain.  Installation of ESR1 LBD in replacement of daf-12 LBD causes restoration of normal pumping phenotype and is offered as ESR1 RediMODEL-KI control strain. A client-specified clinical variant is installed into the ESR1 LBD sequence of the wt-control strain.  The result is a ESR1 RediMODEL-CV strain whose relative phenotypic consequence can be rapidly measured. The CV strain is confirmed by PCR and shipped in the RediMODEL kit format. Included in kit is ESR1 RediMODEL-KO and ESR1 RediMODEL-KI as reference controls.


RediMODEL Kit Details:

Each kit arrives with 3 frozen tubes of ESR1 RediMODEL-CV and 3 tubes of N2 for control and all materials needed for 2+ days of growth.

PLEASE PUT FROZEN TUBES AT -80C UPON ARRIVAL.

Authentication:

Genotype and phenotype data provides a capacity for researcher to monitor and retain authentication, as per NIH guidelines.

Genotype data:

PCR Assay

The RediMODEL-CV line is verified and followed by PCR. The gel image in Genotype Data shows the expected PCR band pattern in an agarose gel for the primer set supplied with the RediMODEL kit.



amplicon size
wild type 500 bp
ESR1 RediMODEL-CV 900 bp
 

Phenotype data:

Bio Assay

The RediMODEL-CV line's activity is best followed by monitoring changes in neurotransmission rates of the food intake. Pharynx pumping increases and decreases are easily monitored in ScreenChip system assay (Nemametrix.com). using the Low Stimulation Pharynx Pumping Protocol (P001), a significant difference in pumping rate is observed.

Low Stimulation Pharynx Pumping Protocol (P001)

strain frequency (Hz)
ESR1 RediMODEL-KO 10%
ESR1 RediMODEL-CV ??%
ESR1 RediMODEL-KI 100%

Discover ESR1 RediMODEL-CV Kit: | $6695 each kit Buy Now

Discover RediMODEL-KI Kit: | $845 each kit

Inquire on ESR1 RediMODEL-KI

Please provide contact info and a company representative will contact you soon with invoicing details

ESR1 rediMODEL-KI inquiry

Discover RediMODEL-CV Kit: | $6695 each kit

Inquire on ESR1 RediMODEL-CV

Please provide contact info and a company representative will contact you soon with invoicing details

ESR1 rediMODEL-CV inquiry

Alignment of ESR1 to daf-12

Alignment Length Identity Similarity Gaps
240 23% 40% 9%

Lets us know if you want to model clinical variants of ESR1 in native daf-12 gene

RediMODEL-KInative - XXXXX with human point mutations