Humanized model organisms are powerful biological models that allow scientists to study human disease genes in simpler contexts without losing the value of in vivo studies.
Video: “Gene-Swap”. The human coding sequence of STXBP1 was inserted into the native locus of C. elegans otholog gene. The worms version of the gene is replaced with a human coding sequence.
The Gene-Swapped STXBP1 sequence functions and shows a significant level of activity (left). In contrast, the knock-out shows very little activity (middle). For the R406H genomic variant, its activity is somewhere in between the “humanized” and “knock-out” strain (right).
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In either C. elegans or Zebrafish, a native model organism gene can be replaced by a human gene with the same biological function. Mutations can be introduced into the human gene in order to make a disease variant. Alternatively, the human gene can be expressed in specific tissues or stages of development (see figure 1 below).
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- Patient Allele Analysis - Functional analysis of patient genomic variants through phenotyping of a model organism to determine pathogenicity.
- C. elegans Phenotype Analysis - Full phenotypic analysis of your C. elegans transgenic and obtain measurements of the functional output of your C. elegans strains.
- Baruah et al. Expression of human Bcl-xL (Ser49) and (Ser62) mutants in Caenorhabditis elegans causes germline defects and aneuploidy. PLoS One. 2017 May 8;12(5):e0177413.
- Piazzesi et al. Replication-Independent Histone Variant H3.3 Controls Animal Lifespan through the Regulation of Pro-longevity Transcriptional Programs. Cell Rep. 2016 Oct 18;17(4):987-996.
Creation of lines that expressed the human version of Bcl-XL
Generating lines that expressed the human version of Bcl-XL, an anti-apoptotic protein enabled the publication of Expression of human Bcl-xL (Ser49) and (Ser62) mutants in Caenorhabditis elegans causes germline defects and aneuploidy by Baruah et al. In addition, a variety of Bcl-XL mutations were also integrated into the genome of the worm by NemaMetrix.
This graph shows reduced progeny production when a variety of Bcl-XL mutants are expressed in worms. Making these mutations in the human Bcl-Xl Serines has a dominant effect on the C. elegans phenotype. Dr. Parker and his colleagues are using these C. elegans strains to better understand Human anti-apoptotic protein function and as a target for drug screening.
Generating line expressing the human H3.3 protein
NemaMetrix built a line expressing the human H3.3 protein enabled Piazzesi et al. to study the H3.3 histone variant in C. elegans. They found the loss of function mutant displayed a strong “bagging” phenotype, where the eggs hatch inside the animal’s body. When they tested these animals they found that the human H3.3 suppressed the bagging phenotype of the mutant.
Below figure illustrates progeny production. The results are published in Replication-Independent Histone Variant H3.3 Controls Animal Lifespan through the Regulation of Pro-longevity Transcriptional Programs. Cell Rep. 2016 Oct 18;17(4):987-996.
|Build Type||Project Steps|
|Step 1: Design ||Step 2: Reagent Building||Step 3: Injection Mix Preparation||Step 4: Injections||Step 5: Initial Screening||Step 6: Confirmation of Transgenic Line(s)||Step 7: Cryopreservation / Authentication|
|Custom Injection Mix|
Pricing (price reflects academic pricing)
|Service Package||Price||Est. Delivery Time|
|Full Build||$5,239 - $6,559||12 - 16 Weeks|
|Candidate Lines||$3,269 - $4,369||8 - 12 Weeks|
|Custom Injection Mix||$1,429 - $1,969||3 - 6 Weeks|