Biology subjects

Waehrisch, S.

Publications and source records attributed to Waehrisch, S..

3 recordsLinked to original sources

bioRxiv2025

Targeted sex ratio distortion in the mouse

In animal breeding, female or male progeny is preferred depending on the use of the animals. Especially in livestock, offspring with undesired sex is of low economic value and often culled. Here we achieve targeted sex ratio distortion in the mouse, leveraging components of a selfish supergene, the t-haplotype. Utilizing its central element, the t-responder, we generate a highly "selfless" genetic element disabling transgenic sperm. When integrated on the X or Y chromosome it results in a high prevalence of non-transgenic offspring of the desired sex. Our strategy overcomes key limitations of existing strategies, including compromised animal health, reduced fertility, and fully transgenic breeding stocks, which might foster acceptance of its application to livestock. The efficacy of our approach marks a groundbreaking advancement in animal breeding. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=130 HEIGHT=200 SRC="FIGDIR/small/660540v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@1b11374org.highwire.dtl.DTLVardef@742ec5org.highwire.dtl.DTLVardef@1aaafc0org.highwire.dtl.DTLVardef@f87dac_HPS_FORMAT_FIGEXP M_FIG C_FIG Transgene integration on X or Y chromosome affects the motility of transgenic sperm resulting in a strong sex-bias towards non-transgenic/wildtype offspring. Application to livestock can reduce unwanted progeny and transform farm animal breeding.

genetics↗

bioRxiv2022

The lncRNA Sweetheart regulates compensatory cardiac hypertrophy after myocardial injury

After myocardial infarction in the adult heart the remaining, non-infarcted tissue adapts to compensate the loss of functional tissue. This adaptation requires changes in gene expression networks, which are mostly controlled by transcription regulating proteins. Long non-coding transcripts (lncRNAs) are now recognized for taking part in fine-tuning such gene programs. We identified and characterized the cardiomyocyte specific lncRNA Sweetheart RNA (Swhtr), an approximately 10 kb long transcript divergently expressed from the cardiac core transcription factor coding gene Nkx2-5. We show that Swhtr is dispensable for normal heart development and function, but becomes essential for the tissue adaptation process after myocardial infarction. Re-expressing Swhtr from an exogenous locus rescues the Swhtr null phenotype. Genes depending on Swhtr after cardiac stress are significantly occupied, and therefore most likely regulated by NKX2-5. Our results indicate a synergistic role for Swhtr and the developmentally essential transcription factor NKX2-5 in tissue adaptation after myocardial injury.

developmental biology↗

bioRxiv2021

Fendrr synergizes with Wnt signalling to regulate fibrosis related genes during lung development

Long non-coding RNAs are a very versatile class of molecules that can have important roles in regulating a cells function, including regulating other genes on the transcriptional level. One of these mechanisms is that RNA can directly interact with DNA thereby recruiting additional components such as proteins to these sites via a RNA:dsDNA triplex formation. We genetically deleted the triplex forming sequence (FendrrBox) from the lncRNA Fendrr in mice and find that this FendrrBox is partially required for Fendrr function in vivo. We find that the loss of the triplex forming site in developing lungs causes a dysregulation of gene programs, associated with lung fibrosis. A set of these genes contain a triplex site directly at their promoter and are expressed in fibroblasts. We confirm the formation of RNA:dsDNA formation with target promoters. We find that Fendrr with the Wnt signalling pathway regulates these genes, implicating that Fendrr synergizes with Wnt signalling in lung fibrosis.

developmental biology↗