RediMODEL transgenics in C. elegans

LRRK2 - leucine-rich repeat kinase

GENE DESCRIPTION:

  • Function: LRRK2 is a leucine-rich repeat kinase necessary for stability of dopaminergic neurons.
  • Disease: Genetic defects in LRRK2 have been found to be highly associated with Parkinson's Disease.
 

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

LRRK2 RediMODEL KO: Generated in the C. elegans homolog lrk-1 is an early gene deletion as a 3-frame STOP allele which leads to loss of gene expression. The resulting lrk-1 deletion knock-out (KO) results in decreased neuronal activity near the pharynx. Major phenotype readout for KO line is an observation of reduced pharynx pumping with exposure to oxidative stress. An 3-frame STOP mutant is currently available for preorder as gene knock-out.

 

LRRK2 RediMODEL KI: Generated in the C. elegans homolog lrk-1 with human gene insertion to create a knock-in (KI) strain. Entire coding of lrk-1 is replaced with wild-type LRRK2 coding sequence. An LRRK2 gene replacement is currently available for preorder as a humanized wt line.

 

LRRK2 RediMODEL CV: Generated in the C. elegans homolog lrk-1 with human gene insertion containing a clinical variant allele to create a clinical variant (CV) strain. Entire coding of lrk-1 is replaced with LRRK2 coding sequence containing amino-acid change polymorphism that has been observed in patient populations. Upon request, an LRRK2 line with client-specific polymorphism is made as a clinical variant allele.

 

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

LRRK2 - leucine-rich repeat kinase

DESCRIPTION:

LRRK2 is a leucine-rich repeat kinase of the cytoplasm whose normal interactions with parkin function are necessary to stabilize dopaminergic neurons. (other names: PARK8, RIPK7, ROCO2, AURA17, DARDARIN)

DISEASES:

Parkinson Disease, Parkinsonian Disorders, Nerve Degeneration, Endometriosis, Renal Cell Carcinoma.*

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

Protein domain - slc6a3 dat-1.png

HOMOLOGY:

Human Gene LRRK2 Alignment         
C. elegans Gene lrk-1 align
Identity 21%
Similarity 37%

KNOCK-OUT of C. elegans gene:

lrk-1 is a homolog gene to LRRK2. The lrk-1 gene functions to control dopaminergic neuron stability. When lrk-1  is expressed and active, it leads to normal resistance to oxidative stress. Deletion mutations in lrk-1  cause sensitivity to oxidative stress loss-of-function phenotype. The canonical allele in lrk-1  is (km17), which contains a small deletion in the C-terminal coding region of lrk-1. The most easily measured phenotype for the deletion allele is a hydrogen peroxide sensitivity phenotype. Because the small deletion has the potential to retain function, an earlier deletion with 3 frame stop in the N-terminus of the lrk-1  locus is used instead. The early deletion allele is offered as the LRRK RediMODEL-KO strain as a 4x outcrossed allele.  The KO strain is confirmed by PCR and shipped in the RediMODEL kit format. Included in each kit is N2 wild-type strain as a reference control.


RediMODEL Kit Details:

Each kit arrives with 3 frozen tubes of LRRK2 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 the researcher to monitor and retain authentication, as per NIH guidelines.

Genotype data:

PCR Assay

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



amplicon size
wild type 500 bp
LRRK2 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 Hydrogen Peroxide Sensitivity (P007), a significant difference in pumping rate can be observed.

Hydrogen Peroxide Sensitivity (P007)


strain wt frequency (Hz)
N2 wild type 100%
LRRK2 RediMODEL-KO 10%

Discover LRRK2 RediMODEL-KO Kit: | $845 each kit Buy Now

Discover RediMODEL-KO Kit: | $845 each kit

Order LRRK2 RediMODEL-KO

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LRRK2 rediMODEL-KO inquiry

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

LRRK2 - leucine-rich repeat kinase

DESCRIPTION:

LRRK2 is a leucine-rich repeat kinase of the cytoplasm whose normal interactions with parkin function are necessary to stabilize dopaminergic neurons. (other names: PARK8, RIPK7, ROCO2, AURA17, DARDARIN)

DISEASES:

Parkinson Disease, Parkinsonian Disorders, Nerve Degeneration, Endometriosis, Renal Cell Carcinoma.*

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

Protein domain - slc6a3 dat-1.png

HOMOLOGY:

Human Gene LRRK2 Alignment         
C. elegans Gene lrk-1 align
Identity 21%
Similarity 37%
RediMODEL-KI logo sml.png

HUMANIZED C. elegans:

lrk-1 is a homolog gene to LRRK2. The lrk-1 gene functions to control dopaminergic neuron stability. When lrk-1  is expressed and active, it leads to normal resistance to oxidative stress. Deletion mutations in lrk-1  cause sensitivity to oxidative stress loss-of-function phenotype measured as an increased hydrogen peroxide sensitivity. To create a sufficient KO model, an early deletion allele is offered as the LRRK RediMODEL-KO strain as a 4x outcrossed allele. To create a humanized worm, the LRRK2 gene is swapped for the lrk-1 coding segment.   Installation of LRRK2 in replacement of lrk-1 causes restoration of normal oxidative stress response phenotype and is offered as LRRK2 RediMODEL-KI strain. The KI strain is confirmed by PCR and shipped in the RediMODEL kit format. Included in each kit is LRRK2 RediMODEL-KO as a reference control.


RediMODEL Kit Details:

Each kit arrives with 3 frozen tubes of LRRK2 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 the researcher to monitor and retain authentication, as per NIH guidelines.

Genotype data:

PCR Assay

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

amplicon size
wild type 500 bp
LRRK2 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 Hydrogen Peroxide Sensitivity (P007), a significant difference in pumping rate can be observed.

Hydrogen Peroxide Sensitivity (P007)

strain wt frequency (Hz)
LRRK2 RediMODEL-KO 10%
LRRK2 RediMODEL-KI 100%

Discover LRRK2 RediMODEL-KI Kit: | $845 each kit Buy Now

Discover RediMODEL-KI Kit: | $845 each kit

Inquire on LRRK2 RediMODEL-KI

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

LRRK2 rediMODEL-KI inquiry

RediMODEL clinical variant in C. elegans | $6695 each kit Buy Now

LRRK2 - leucine-rich repeat kinase

DESCRIPTION:

LRRK2 is a leucine-rich repeat kinase of the cytoplasm whose normal interactions with parkin function are necessary to stabilize dopaminergic neurons. (other names: PARK8, RIPK7, ROCO2, AURA17, DARDARIN)

DISEASES:

Parkinson Disease, Parkinsonian Disorders, Nerve Degeneration, Endometriosis, Renal Cell Carcinoma.*

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

Protein domain - slc6a3 dat-1.png

HOMOLOGY:

Human Gene LRRK2 Alignment         
C. elegans Gene lrk-1 align
Identity 21%
Similarity 37%
rediMODEL-KO

CLINICAL VARIANT C. elegans:

lrk-1 is a homolog gene to LRRK2. The lrk-1 gene functions to control dopaminergic neuron stability. When lrk-1  is expressed and active, it leads to normal resistance to oxidative stress. Deletion mutations in lrk-1  cause sensitivity to oxidative stress loss-of-function phenotype measured as an increased hydrogen peroxide sensitivity. To create a sufficient KO model, an early deletion allele is offered as the LRRK RediMODEL-KO strain as a 4x outcrossed allele. To create a humanized worm, the LRRK2 gene is swapped for the lrk-1 coding segment to create LRRK2 RediMODEL-KI control strain.  A client-specified clinical variant is installed into the LRRK2 sequence of the wt-control strain.  The result is an LRRK2 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 each kit are LRRK2 RediMODEL-KO and LRRK2 RediMODEL-KI as reference controls.


RediMODEL Kit Details:

Each kit arrives with 3 frozen tubes of LRRK2 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 the researcher to monitor and retain authentication, as per NIH guidelines.

Genotype data:

PCR Assay

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



amplicon size
wild type 500 bp
LRRK2 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 Hydrogen Peroxide Sensitivity (P007), a significant difference in pumping rate can be observed.

Hydrogen Peroxide Sensitivity (P007)

strain frequency (Hz)
LRRK2 RediMODEL-KO 10%
LRRK2 RediMODEL-CV ??%
LRRK2 RediMODEL-KI 100%

Discover LRRK2 RediMODEL-CV Kit: | $6695 each kit Buy Now

Discover RediMODEL-CV Kit: | $6695 each kit

Inquire on LRRK2 RediMODEL-CV

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

LRRK2 rediMODEL-CV inquiry

Alignment of LRRK2 to irk-1

Alignment Length Identity Similarity Gaps
2620 21% 37% 33%

Lets us know if you want to model clinical variants of LRRK2 in native lrk-1 gene

RediMODEL-KInative - lrk-1 with human point mutations