RRC ID |
59637
|
Author |
Zhao Y, Wang H, Poole RJ, Gems D.
|
Title |
A fln-2 mutation affects lethal pathology and lifespan in C. elegans.
|
Journal |
Nat Commun
|
Abstract |
Differences in genetic background in model organisms can have complex effects on phenotypes of interest. We previously reported a difference in hermaphrodite lifespan between two wild-type lines widely used by C. elegans researchers (N2 hermaphrodite and male stocks). Here, using pathology-based approaches and genome sequencing, we identify the cause of this difference as a nonsense mutation in the filamin gene fln-2 in the male stock, which reduces early mortality caused by pharyngeal infection. We show how fln-2 variation explains previous discrepancies involving effects of sir-2.1 (sirtuin deacetylase) on ageing, and show that in a fln-2(+) background, sir-2.1 over-expression causes an FUDR (DNA synthesis inhibitor)-dependent reduction in pharyngeal infection and increase in lifespan. In addition we show how fln-2 variation confounds effects on lifespan of daf-2 (insulin/IGF-1 signalling), daf-12 (steroid hormone signalling), and eat-2 (putative dietary restriction). These findings underscore the importance of identifying and controlling genetic background variation.
|
Volume |
10(1)
|
Pages |
5087
|
Published |
2019-11-8
|
DOI |
10.1038/s41467-019-13062-z
|
PII |
10.1038/s41467-019-13062-z
|
PMID |
31704915
|
PMC |
PMC6841690
|
MeSH |
Animals
Caenorhabditis elegans / genetics*
Caenorhabditis elegans Proteins / genetics
Codon, Nonsense
Epistasis, Genetic / genetics*
Filamins / genetics*
Genetic Background
Hermaphroditic Organisms
Longevity / genetics*
Male
Models, Animal
Pharyngitis / genetics*
Pharyngitis / mortality
Receptor, Insulin / genetics
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Nicotinic / genetics
Sirtuins
|
IF |
11.878
|
Times Cited |
3
|
Resource |
C.elegans |
tm4687 |