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New public serverarXiv bioRxivleoXIV

New public server

arXiv
bioRxiv
leoXIV

So while our initial hypothesis was not correct, making the allelic series allowed us to identify new phenotypes (cerebellum expansion,...

So while our initial hypothesis was not correct, making the allelic series allowed us to identify new phenotypes (cerebellum expansion, age-dependent weight gain), threshold effects, age-dependence, and graded responses across several affected organs. The “one-pot” editing approach to create the quantitative series should be applicable to other genes. (3 more in the pipeline...). 7/7

Other phenotypes showed a graded response to Tulp3 expression level. The lowest viable expression level we tested had ~5-6% increase in...

Other phenotypes showed a graded response to Tulp3 expression level. The lowest viable expression level we tested had ~5-6% increase in cerebellum size. Up to 10% of normal Tulp3 level resulted in excess body weight and adiposity. Increments up to ~50% showed expression- and age-dependent cystic index in both kidneys. 6/

Complete Tulp3 exon 7 deletion results in a frameshift and is 100% embryonic lethal, with polydactyly and neural tube defects as reported in...

Complete Tulp3 exon 7 deletion results in a frameshift and is 100% embryonic lethal, with polydactyly and neural tube defects as reported in previous ko models. But <5% of normal Tulp3 expression is enough for normal viability and digit formation. By contrast deletion of exon 4, which is conserved but maintains reading frame, is fully viable. 5/

Sadly, no. But to test it, knowing that Tulp3 knockouts are lethal in mice, we made a graded hypomorphic series by targeting the...

Sadly, no. But to test it, knowing that Tulp3 knockouts are lethal in mice, we made a graded hypomorphic series by targeting the polypyrimidine tract at the splice acceptor site upstream to an essential exon (exon 7). A range of pyrimidine to purine substitutions and indels created a quantitative allelic series that express allele-specific levels of Tulp3 RNA and protein. This let us look at quantitative requirements across multiple phenotypes in a coisogenic background and shared environment 4/

Several years ago, Chen-Jei Hong in my lab showed that Tulp3 was a repressive target of Zfp423, a transcription factor required for Shh...

Several years ago, Chen-Jei Hong in my lab showed that Tulp3 was a repressive target of Zfp423, a transcription factor required for Shh mitogenic response by ex vivo granule progenitors. In a transformed cell model expressing fluorescent Smo, simultaneous knockdown of both Zfp423 and Tulp3 partially reversed loss of Smo translocation caused by Zfp423 kd alone. But would that be enough to suppress Zfp423 vermis hypoplasia in vivo?
https://doi.org/10.1371/journal.pgen.1006357 2/

How much genetic function is required to avoid the worst phenotypes? For Tulp3, the answers may surprise you! New pre-print from my lab, led...

How much genetic function is required to avoid the worst phenotypes? For Tulp3, the answers may surprise you! New pre-print from my lab, led by postdoc Corinne McCoy, using an 8-part genotypic series in mice. #Tootorial https://www.biorxiv.org/content/10.1101/2025.04.25.650726v1 1/

Norman was emeritus when I started grad school, but still active in seminars and journal club. He was kind to me and communicated my first...

Norman was emeritus when I started grad school, but still active in seminars and journal club. He was kind to me and communicated my first paper to PNAS.

Remembering Norman Horowitz, born #OTD 1915. A pioneering biochemical geneticist, he showed step-wise arginine metabolism and coined the...

Remembering Norman Horowitz, born #OTD 1915.
A pioneering biochemical geneticist, he showed step-wise arginine metabolism and coined the term “one gene one enzyme hypothesis” with Beadle and Tatum. Later chief biologist at JPL to test signs of life on Mars.
oralhistories.library.caltech.edu/22/

Bee on lavender, 2025#SilentSunday

Bee on lavender, 2025
#SilentSunday

“Research is endlessly seductive, but writing is hard work.”- Barbara W. Tuchman

“Research is endlessly seductive, but writing is hard work.”
- Barbara W. Tuchman

For #ThrowbackThursday here is the US constitution, via the National Archives.https://www.archives.gov/founding-docs/constitution-transcript

For #ThrowbackThursday here is the US constitution, via the National Archives.

https://www.archives.gov/founding-docs/constitution-transcript

#SilentSunday

#SilentSunday

“What are you going to believe: his well-documented, decades-long record, or the thing he said today when he was trying to get a job?”...

“What are you going to believe: his well-documented, decades-long record, or the thing he said today when he was trying to get a job?” — Michael Kosta

Most of the AI being pushed into everyday applications are like that annoying acquaintance who keeps trying to finish your sentences without...

Most of the AI being pushed into everyday applications are like that annoying acquaintance who keeps trying to finish your sentences without the slightest idea what you are talking about.

#SilentSunday

#SilentSunday

Saying that NIH and NSF should fund only projects with obvious immediate impact is like saying the water department should fund only...

Saying that NIH and NSF should fund only projects with obvious immediate impact is like saying the water department should fund only faucets.

“Power invariably means both responsibility and danger. Our forefathers faced cetain perils which we have outgrown. We now face other...

“Power invariably means both responsibility and danger. Our forefathers faced cetain perils which we have outgrown. We now face other perils, the very existence of which it was impossible that they should foresee. Modern life is both complex and intense, and the tremendous changes wrought by the extraordinary industrial development of the last half-century are felt in every fibre of our social and political being.”
Theodore Roosevelt
March 4, 1905
#inauguration

https://theodorerooseveltcenter.org/Research/Digital-Library/Record/Pdf?url=https://theodorerooseveltcenter.s3.amazonaws.com/TRC/TRAJ/1600/V016/N4/TRAJ016_4_A.pdf

“Recognition of the falsity of material wealth as the standard of success goes hand in hand with the abandonment of the false belief that...

“Recognition of the falsity of material wealth as the standard of success goes hand in hand with the abandonment of the false belief that public office and high political position are to be valued only by the standards of pride of place and personal profit”
Franklin D. Roosevelt
January 20, 1933
#inauguration
www.presidency.ucsb.edu/documents/in...

“The enemies of this faith know no god but force, no devotion but its use. They tutor men in treason. They feed upon the hunger of others....

“The enemies of this faith know no god but force, no devotion but its use. They tutor men in treason. They feed upon the hunger of others. Whatever defies them, they torture, especially the truth.”
Eisenhower #inauguration