title: Modifier genes for mouse phosphatidylinositol transfer protein α (vibrator) that bypass juvenile lethality.
abstract: Phosphatidylinositol transfer proteins (PITPs) mediate lipid signaling and membrane trafficking in eukaryotic cells. Loss-of-function mutations of the gene encoding PITPα in mice result in a range of dosage-sensitive phenotypes, including neurological dysfunction, neurodegeneration, and premature death. We have previously reported genetic suppression of a strong hypomorphic allele, vibrator, by a wild-derived variant of Nxf1, which increases the level of PITPα made from vibrator alleles and suppresses each of the neurological and survival phenotypes. Here we report discovery and genetic mapping of additional vibrator modifiers, Mvb2 and Mvb3, from a different strain background that suppresses juvenile lethality without suppressing visible phenotypes or gene expression. Genotype-specific survival analysis predicts molecular heterosis at Mvb3. These results indicate a mechanism of suppression that bypasses a quantitative requirement for PITPα function.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, California 92093-0644, USA.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Concepcion
authors.forename: Frank
authors.initials: F
authors.lastname: Johannes
authors.forename: Yuan Hung
authors.initials: YH
authors.lastname: Lo
authors.forename: Jay
authors.initials: J
authors.lastname: Yao
authors.forename: Jerry
authors.initials: J
authors.lastname: Fong
authors.forename: Bruce A
authors.initials: BA
authors.lastname: Hamilton
mesh_terms: D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005838:Genotype; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D009410:Nerve Degeneration / Q000235:genetics; D010641:Phenotype; D049294:Phospholipid Transfer Proteins / Q000235:genetics* / Q000378:metabolism*; D040641:Quantitative Trait Loci; D015398:Signal Transduction / Q000235:genetics; D013489:Suppression, Genetic
chemical_list: D049294:Phospholipid Transfer Proteins; C493468:Pitpn protein, mouse