RediMODEL transgenics in C. elegans

DMD - dystrophin

GENE DESCRIPTION:

  • Function: DMD is a connective protein critical for linking muscle fibers to the plasma membrane of muscle cells.
  • Disease: Genetic defects in DMD have been found to be highly associated with Duchene Muscular Dystrophy.
 

Products:

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

rediMODEL-KO

DMD RediMODEL KO: Generated in the C. elegans homolog dys-1 is a 3-frame-stop inserted in the last 1/3rd of sequence. The result is a loss of function allele in the dys-1 gene. Major phenotype readout is the observation of increased pharynx pumping frequency relative to wild type. The 3-frame-stop allele is currently available as gene knock-out.

 

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

 

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

 

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

DMD - dystrophin

DESCRIPTION:

DMD is a connective protein critical for linking muscle fibers to the plasma membrane of muscle cells. (Other names: BMD, CMD3B, DXS142, DXS164, DXS206, DXS230, DXS239, DXS268, DXS269, DXS270, DXS272, MRX85)

DISEASES:

Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, Dmd-Associated Dilated Cardiomyopathy, Muscular Dystrophy, Status Epilepticus, Dilated Cardiomyopathy, Cardiomyopathies, Embryonal Rhabdomyosarcoma, Gastrointestinal Stromal Tumors, Necrosis, Neoplasm Invasiveness, Neoplasm Metastasis, Polycystic Ovary Syndrome, leiomyosarcoma, Cardiomegaly, Ventricular Dysfunction, Calcinosis.*

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

Protein domain - slc6a3 dat-1.png

HOMOLOGY:

Human Gene DMD Alignment         
C. elegans Gene dys-1 align
Identity 24%
Similarity 41%

KNOCK-OUT of C. elegans gene:

dys-1 is the homolog gene to DMD. The dys-1 gene functions to control contraction of muscle fibers. When dys-1 is expressed and active, it enables pharynx muscle contraction. Deletion mutations in dys-1  as DMD RediMODEL-KO causes a loss-of-function phenotype as an elevated pumping rate upon mild stimulation with food. The canonical allele in dys-1 is (cx18), which has not yet been mapped to the genome. The most easily measured phenotype of (cx18) is a mild pharynx pumping loss-of-function phenotype. Because the (cx18) allele has unknown potential to retain function, a targeted 3-frame STOP insertion in a conserved domain early in second half of dys-1 locus is used instead. The 3-frame STOP allele is offered as the DMD RediMODEL-KO strain as a 4x outcrossed allele. The KO strain is confirmed by PCR and shipped in the RediMODEL kit format.  Included in the kit is N2 wild-type strain as a reference control.

genomic locus - dys-1 KO.png

RediMODEL Kit Details:

Each kit arrives with 3 frozen tubes of DMD 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 sequence 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 used for verification of the RediMODEL kit.



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

Phenotype data:

Bio Assay

The RediMODEL-KO line's activity is best followed by monitoring changes in neurotransmission rates of food intake. Pharynx pumping increases and decreases are easily monitored in the 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%
DMD RediMODEL-KO 10%

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

Discover RediMODEL-KO Kit: | $845 each kit

Inquire on DMD RediMODEL-KO

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

DMD rediMODEL-KO inquiry

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

DMD - dystrophin

DESCRIPTION:

DMD is a connective protein critical for linking muscle fibers to the plasma membrane of muscle cells. (Other names: BMD, CMD3B, DXS142, DXS164, DXS206, DXS230, DXS239, DXS268, DXS269, DXS270, DXS272, MRX85)

DISEASES:

Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, Dmd-Associated Dilated Cardiomyopathy, Muscular Dystrophy, Status Epilepticus, Dilated Cardiomyopathy, Cardiomyopathies, Embryonal Rhabdomyosarcoma, Gastrointestinal Stromal Tumors, Necrosis, Neoplasm Invasiveness, Neoplasm Metastasis, Polycystic Ovary Syndrome, leiomyosarcoma, Cardiomegaly, Ventricular Dysfunction, Calcinosis.*

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

Protein domain - slc6a3 dat-1.png

HOMOLOGY:

Human Gene DMD Alignment         
C. elegans Gene dys-1 align
Identity 24%
Similarity 41%
RediMODEL-KI logo sml.png

HUMANIZED C. elegans:

dys-1 is the homolog gene to DMD. The dys-1 gene functions to control contraction of muscle fibers. When dys-1 is expressed and active, it enables pharynx muscle contraction. Deletion mutations in dys-1  as DMD RediMODEL-KO cause a loss-of-function phenotype as an elevated pumping rate upon mild stimulation with food. To create a humanized worm, DMD gene is swapped for the dys-1 coding segment.   Installation of DMD in replacement of dys-1 causes restoration of normal pharynx pumping phenotype and is offered as DMD RediMODEL-KI. The KI strain is confirmed by PCR and shipped in the RediMODEL kit format. Included in the kit is DMD RediMODEL-KO as a reference control.


RediMODEL Kit Details:

Each kit arrives with 3 frozen tubes of DMD 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 sequence 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 used to verify the RediMODEL kit.

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

Phenotype data:

Bio Assay

The RediMODEL-KI line's activity is best followed by monitoring changes in neurotransmission rates of food intake. Pharynx pumping increases and decreases are easily monitored in the 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)
DMD RediMODEL-KO 10%
DMD RediMODEL-KI 100%

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

Discover RediMODEL-KI Kit: | $845 each kit

Inquire on DMD RediMODEL-KI

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

DMD rediMODEL-KI inquiry

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

DMD - dystrophin

DESCRIPTION:

DMD is a connective protein critical for linking muscle fibers to the plasma membrane of muscle cells. (Other names: BMD, CMD3B, DXS142, DXS164, DXS206, DXS230, DXS239, DXS268, DXS269, DXS270, DXS272, MRX85)

DISEASES:

Duchenne Muscular Dystrophy, Becker Muscular Dystrophy, Dmd-Associated Dilated Cardiomyopathy, Muscular Dystrophy, Status Epilepticus, Dilated Cardiomyopathy, Cardiomyopathies, Embryonal Rhabdomyosarcoma, Gastrointestinal Stromal Tumors, Necrosis, Neoplasm Invasiveness, Neoplasm Metastasis, Polycystic Ovary Syndrome, leiomyosarcoma, Cardiomegaly, Ventricular Dysfunction, Calcinosis.*

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

Protein domain - slc6a3 dat-1.png

HOMOLOGY:

Human Gene DMD Alignment         
C. elegans Gene dys-1 align
Identity 24%
Similarity 41%
rediMODEL-KO

CLINICAL VARIANT C. elegans:

dys-1 is the homolog gene to DMD. The dys-1 gene functions to control muscle contraction. When dys-1 is expressed and active, it enables pharynx muscle contraction. Deletion mutation in dys-1 as a DMD RediMODEL-KO causes a loss-of-function phenotype as an elevated pumping rate upon mild stimulation with food. Installation of DMD in replacement of dys-1 results in the DMD RediMODEL-KI control strain and cause restoration of the normal pharynx pumping phenotype.  A client-specified clinical variant is installed into the DMD sequence of the wt-control strain.  The result is a DMD 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 the kit are DMD RediMODEL-KO and DMD RediMODEL-KI as reference controls.


RediMODEL Kit Details:

Each kit arrives with 3 frozen tubes of DMD 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 sequence 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 used to verify the RediMODEL kit.



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

Phenotype data:

Bio Assay

The RediMODEL-CV line's activity is best followed by monitoring changes in neurotransmission rates of food intake. Pharynx pumping increases and decreases are easily monitored in the 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)
DMD RediMODEL-KO 10%
DMD RediMODEL-CV ??%
DMD RediMODEL-KI 100%

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

Discover RediMODEL-CV Kit: | $6695 each kit

Inquire on DMD RediMODEL-CV

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

DMD rediMODEL-CV inquiry

Alignment of DMD to dys-1

Alignment Length Identity Similarity Gaps
4160 24% 41% 24%

Lets us know if you want to model clinical variants of DMD in the native dys-1 gene.

RediMODEL-KI native - dys-1 with human point mutations