RediMODEL transgenics in C. elegans

UNC13A - synaptic vesicle release regulator

GENE DESCRIPTION:

  • Function: UNC13A is needed for coordinated neurotransmitter release at synapses.
  • Disease: Genetic defects in UNC13A have been found to be highly associated with Amyotrophic Lateral Sclerosis (ALS).
 

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

UNC13A RediMODEL KO: Generated in the C. elegans homolog unc-13 with framshifting microdeleltion (s69) creates a knock-out (KO) strain by eliminating coding for a significant portion of the last half of the gene. Loss of function from unc-13 frameshift mutation leads to uncoordinated movement. Major phenotype readout is the observation of deviation in pharyngeal pumping. An outcrossed version of (s69) frameshifting SNP is currently available for preorder as gene knock-out.

 

UNC13A RediMODEL KI: Generated in the C. elegans homolog unc-13 with human gene insertion to create a knock-in (KI) strain. Entire conserved coding of unc-13 is replaced with wild-type UNC13A coding sequence. A UNC13A gene replacement is available for preorder as a humanized wt line.

 

UNC13A RediMODEL CV: Generated in the C. elegans homolog unc-13 with human gene insertion containing a clinical variant allele to create a clinical-variant (CV) strain. Entire coding of unc-13 is replaced with UNC13A coding sequence containing an amino-acid change polymorphism that has been observed in patient populations. Upon request, a UNC13A point-mutant line with a client-specific polymorphism is made as a clinical variant allele.

 

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

UNC13A - synaptic vesicle release regulator

DESCRIPTION:

UNC13 family proteins bind to phorbol esters and diacylglycerol and play important roles in coordinated neurotransmitter release at synapses. Polymorphisms in UNC13A are risk factors for sporadic amyotrophic lateral sclerosis. (other names: Munc13-1)

DISEASES:

Amyotrophic Lateral Sclerosis.*

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

Protein domain - slc6a3 dat-1.png

HOMOLOGY:

Human Gene UNC13A Alignment         
C. elegans Gene unc-13 align
Identity 41%
Similarity 54%

KNOCK-OUT of C. elegans gene:

unc-13 is a homolog gene to UNC13A. The unc-13 gene functions to control synaptic vesicle release. When unc-13 is expressed and active, it allows for coordinated movement and regular pharyngeal pumping. Deletion mutations in unc-13 cause pharyngeal pumping irregularities as a loss-of-function phenotype. The canonical allele in unc-13 is (s69), which contains a small deletion in the conserved gene coding region and is thought to render a knock-out (KO) of gene function. The most easily measured phenotype for the KO is a pharyngeal pumping loss-of-function phenotype. To decrease the risk of background mutations, the KO strain is 4x outcrossed. The resulting outcrossed strain containing (s69) allele is offered as the UNC13A RediMODEL-KO strain. 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.


RediMODEL Kit Details:

Each kit arrives with 3 frozen tubes of UNC13A 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 to verify the RediMODEL kit.



amplicon size
wild type 500 bp
UNC13A 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%
UNC13A RediMODEL-KO 10%

Discover UNC13A RediMODEL-KO Kit: | $845 each kit Buy Now

Discover RediMODEL-KO Kit: | $845 each kit

Inquire on UNC13A RediMODEL-KO

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

UNC13A rediMODEL-KO inquiry

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

UNC13A - synaptic vesicle release regulator

DESCRIPTION:

UNC13 family proteins bind to phorbol esters and diacylglycerol and play important roles in coordinated neurotransmitter release at synapses. Polymorphisms in UNC13A are risk factors for sporadic amyotrophic lateral sclerosis. (other names: Munc13-1)

DISEASES:

Amyotrophic Lateral Sclerosis.*

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

Protein domain - slc6a3 dat-1.png

HOMOLOGY:

Human Gene UNC13A Alignment         
C. elegans Gene unc-13 align
Identity 41%
Similarity 54%
RediMODEL-KI logo sml.png

HUMANIZED C. elegans:

unc-13 is a homolog gene to UNC13A. The unc-13 gene functions to control synaptic vesicle release. When unc-13 is expressed and active, it allows for coordinated movement and regular pharyngeal pumping. Deletion mutations in unc-13 cause pharyngeal pumping irregularities as a loss-of-function phenotype.  To create a humanized worm, UNC13A gene is swapped for the unc-13 coding segment.  Installation of UNC13A in replacement of unc-13 causes restoration of normal pharyngeal pumping phenotype and is offered as UNC13A RediMODEL-KI. The KI strain is confirmed by PCR and shipped in the RediMODEL kit format. Included in the kit is UNC13A RediMODEL-KO as a reference control.


RediMODEL Kit Details:

Each kit arrives with 3 frozen tubes of UNC13A 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
UNC13A 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)
UNC13A RediMODEL-KO 10%
UNC13A RediMODEL-KI 100%

Discover UNC13A RediMODEL-KI Kit: | $845 each kit Buy Now

Discover RediMODEL-KI Kit: | $845 each kit

Inquire on UNC13A RediMODEL-KI

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

UNC13A rediMODEL-KI inquiry

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

UNC13A - synaptic vesicle release regulator

DESCRIPTION:

UNC13 family proteins bind to phorbol esters and diacylglycerol and play important roles in coordinated neurotransmitter release at synapses. Polymorphisms in UNC13A are risk factors for sporadic amyotrophic lateral sclerosis. (other names: Munc13-1)

DISEASES:

Amyotrophic Lateral Sclerosis.*

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

Protein domain - slc6a3 dat-1.png

HOMOLOGY:

Human Gene UNC13A Alignment         
C. elegans Gene unc-13 align
Identity 41%
Similarity 54%
rediMODEL-KO

CLINICAL VARIANT C. elegans:

unc-13 is a homolog gene to UNC13A. The unc-13 gene functions to control synaptic vesicle release. When unc-13 is expressed and active, it allows for coordinated movement and regular pharyngeal pumping. Deletion mutations in unc-13 causes pharyngeal pumping irregularities as a loss-of-function phenotype.  Installation of UNC13A in replacement of unc-13  results in the UNC13A RediMODEL-KI control strain and causes restoration of normal pharyngeal pumping phenotype.  A client-specified clinical variant is installed into the UNC13A sequence of the wt-control strain.  The result is a UNC13A 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 kits are UNC13A RediMODEL-KO and UNC13A RediMODEL-KI as reference controls.

genomic locus - UNC13A CV.png

RediMODEL Kit Details:

Each kit arrives with 3 frozen tubes of UNC13A 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
UNC13A 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)
UNC13A RediMODEL-KO 10%
UNC13A RediMODEL-CV ??%
UNC13A RediMODEL-KI 100%

Discover UNC13A RediMODEL-CV Kit: | $6695 each kit Buy Now

Discover RediMODEL-CV Kit: | $6695 each kit

Inquire on UNC13A RediMODEL-CV

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

UNC13A rediMODEL-CV inquiry

Alignment of UNC13A to unc-13

Alignment Length Identity Similarity Gaps
2205 41% 54% 27%

Lets us know if you want to model clinical variants of UNC13A in the native unc-13 gene.

RediMODEL-KInative - unc-13 with human point mutations