Obesity, hyperphagia and increased metabolic efficiency in Pc1 mutant mice
Open accessAbstract
Prohormone convertase 1 (PC1) mutations lead to obesity in humans. However, Pc1 knockout mice do not become obese; in fact, they are runted due to a defect in growth-hormone releasing hormone processing, leading to the speculation that PC1 subserves different functions between mouse and human. Here, we report a novel allele of mouse Pc1 (N222D) that leads to obesity, abnormal proinsulin processing and multiple endocrinological defects. Increased energy intake and a more efficient metabolism contribute to the obesity in Pc1(N222D/N222D) mice. Defective proinsulin processing leads to glucose intolerance, but neither insulin resistance nor diabetes develop despite obesity. The obesity is associated with impaired autocatalytic activation of mature PC1 and reduced hypothalamic alpha-MSH. This is the first characterization of Pc1 mutation in a model organism that mimics human PC1 deficiency.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mice homozygous for an Asn222Asp NEC 1 substitution, which is also within the catalytic domain of the enzyme, are obese and have decreased fertility.
“Accordingly, mice homozygous for an Asn222Asp NEC 1 substitution, which is also within the catalytic domain of the enzyme, are obese and have decreased fertility.69”
From The genetic and molecular basis of idiopathic hypogonadotropic hypogonadism (2009) · cites this paper as [69]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 43 · Cited by 142
- Authors
- Lloyd, D. J., Bohan, S., & Gekakis, N.
- Affiliations
- Genomics Institute of the Novartis Research Foundation (US)
- Corresponding author
- Lloyd, David J.
- ORCID
- Lloyd, David J.
- Venue
- Human Molecular Genetics
- Publisher
- Oxford University Press (OUP)
- Published
- 2006-04-27
- Volume
- 15
- Issue
- 11
- Pages
- 1884-1893
- ISSN
- 0964-6906 (ISSN-L)
- 1460-2083
- OpenAlex
- W2104102520
- Cited by
- 142
- References
- 43
- Citations by year
- 2026: 2 · 2025: 6 · 2023: 1 · 2022: 7 · 2021: 7 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 2 · 2016: 10 · 2015: 7 · 2014: 10 · 2013: 10 · 2012: 9
- FWCI
- 4.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Human Molecular Genetics (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- prohormone convertase 1, obesity, hyperphagia, metabolic efficiency, proinsulin processing, impaired glucose tolerance, growth hormone-releasing hormone, autocatalytic activation, energy intake
- MeSH terms
- Amino Acid Sequence, Animals, Glucose, Humans, Hyperphagia, Hypothalamus, Insulin, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Mutation, Obesity, Sequence Homology, Amino Acid, Proprotein Convertase 1, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
