Evidence map›Paper›PMID 22912808›Full record

ArticlePloS one2012

Pla2g12b and Hpn are genes identified by mouse ENU mutagenesis that affect HDL cholesterol.

Aleksandra Aljakna, Seungbum Choi, Holly Savage, Rachael Hageman Blair, Tongjun Gu, Karen L Svenson, Gary A Churchill, Matt Hibbs, Ron Korstanje

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.1field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

16 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Hepsin enhances liver metabolism and inhibits adipocyte browning in mice.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Aleksandra AljaknaThe Jackson Laboratory, Bar Harbor, Maine, United States of America.
Seungbum Choi
Holly Savage
Rachael Hageman Blair
Tongjun Gu
Karen L Svenson
Gary A Churchill
Matt Hibbs
Ron Korstanje
Jackson Laboratory · USKlinikum rechts der Isar · DE

Funding

Shared Resource ManagementP30CA034196 · NCI · JACKSON LABORATORY · PI Anna Karolina Palucka · 1985 to 2026
$61.9M
UNC and PERLEGEN, IncP50GM076468 · NIGMS · JACKSON LABORATORY · PI SVENSON, KAREN L · 2006 to 2015
$31.0M
Mapping Gene Mutations That Alter HDL Cholesterol Levels in MiceR01HL095668 · NHLBI · JACKSON LABORATORY · PI KORSTANJE, RONNY · 2009 to 2013
$2.4M
Bayesian Dynamic Genome Scale Modeling of HDL Cholesterol TransportF32HL095240 · NHLBI · JACKSON LABORATORY · PI HAGEMAN, RACHAEL · 2009 to 2011
$135k
NCI NIH HHS CA034196NCI NIH HHS P30 CA034196NHLBI NIH HHS 1F32 HL095240NHLBI NIH HHS F32 HL095240NHLBI NIH HHS HL095668NHLBI NIH HHS R01 HL095668NIGMS NIH HHS GM076468NIGMS NIH HHS P50 GM076468
6 · The paper itself

Abstract

Despite considerable progress understanding genes that affect the HDL particle, its function, and cholesterol content, genes identified to date explain only a small percentage of the genetic variation. We used N-ethyl-N-nitrosourea mutagenesis in mice to discover novel genes that affect HDL cholesterol levels. Two mutant lines (Hlb218 and Hlb320) with low HDL cholesterol levels were established. Causal mutations in these lines were mapped using linkage analysis: for line Hlb218 within a 12 Mbp region on Chr 10; and for line Hlb320 within a 21 Mbp region on Chr 7. High-throughput sequencing of Hlb218 liver RNA identified a mutation in Pla2g12b. The transition of G to A leads to a cysteine to tyrosine change and most likely causes a loss of a disulfide bridge. Microarray analysis of Hlb320 liver RNA showed a 7-fold downregulation of Hpn; sequencing identified a mutation in the 3' splice site of exon 8. Northern blot confirmed lower mRNA expression level in Hlb320 and did not show a difference in splicing, suggesting that the mutation only affects the splicing rate. In addition to affecting HDL cholesterol, the mutated genes also lead to reduction in serum non-HDL cholesterol and triglyceride levels. Despite low HDL cholesterol levels, the mice from both mutant lines show similar atherosclerotic lesion sizes compared to control mice. These new mutant mouse models are valuable tools to further study the role of these genes, their affect on HDL cholesterol levels, and metabolism.

Indexed as

EthylnitrosoureaGenetic VariationModels, AnimalAlkaline PhosphataseAnalysis of VarianceAnimalsAntisense Elements (Genetics)Blotting, NorthernBlotting, WesternCholesterol, HDLChromosome MappingCrosses, GeneticEvoked Potentials, Auditory, Brain StemHigh-Throughput Nucleotide SequencingLipidsLod ScoreAlkaline PhosphataseAntisense Elements (Genetics)Cholesterol, HDLEthylnitrosoureahepsinLipidsPhospholipases A2Serine EndopeptidasesThyroxine

Identifiers

PMID22912808
PMCPMC3422231
OpenAlexW2042514398

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.