Normal plasma lipoproteins and fertility in gene-targeted mice homozygous for a disruption in the gene encoding very low density lipoprotein receptor.
Open accessAbstract
The very low density lipoprotein (VLDL) receptor is a recently cloned member of the low density lipoprotein (LDL) receptor family that mediates the binding and uptake of VLDL when overexpressed in animal cells. Its sequence is 94% identical in humans and rabbits and 84% identical in humans and chickens, implying a conserved function. Its high level expression in muscle and adipose tissue suggests a role in VLDL triacylglycerol delivery. Mutations in the chicken homologue cause female sterility, owing to impaired VLDL and vitellogenin uptake during egg yolk formation. We used homologous recombination in mouse embryonic stem cells to produce homozygous knockout mice that lack immunodetectable VLDL receptors. Homozygous mice of both sexes were viable and normally fertile. Plasma levels of cholesterol, triacylglycerol, and lipoproteins were normal when the mice were fed normal, high-carbohydrate, or high-fat diets. The sole abnormality detected was a modest decrease in body weight, body mass index, and adipose tissue mass as determined by the weights of epididymal fat pads. We conclude that the VLDL receptor is not required for VLDL clearance from plasma or for ovulation in mice.
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VLDLR-KO mice exhibited a reduction in mass and BMI relative to WT controls on a mixed background.
“One of the initial observations made by Herz and colleagues when they developed the VLDLR-KO mice was that the mice exhibited a reduction in mass and BMI relative to WT controls on a mixed background27.”
From IDOL regulates systemic energy balance through control of neuronal VLDLR expression (2019) · cites this paper as [27]
The Abstract reports that the authors produced VLDLR-knockout mice and detected a modest decrease in body weight and body mass index. Our copy does not specify a mixed genetic background or explicitly identify wild-type controls for that comparison. (LLM, conf=0.86)
Experimental — accuracy not yet measuredWhole-body deletion of VLDLR is protective against diet-induced obesity.
“Whole body deletion of VLDLR has previously been shown to be protective against diet-induced obesity22,27,28.”
From IDOL regulates systemic energy balance through control of neuronal VLDLR expression (2019) · cites this paper as [27]
The Abstract reports that mice lacking VLDL receptors had modestly lower body weight, body mass index, and adipose tissue mass. It mentions high-fat feeding but does not report that deletion specifically protected against diet-induced obesity, so the diet-specific claim goes beyond the passage. (LLM, conf=0.86)
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- Authors
- Frykman, P. K., Brown, M. S., Yamamoto, T., Goldstein, J. L., & Herz, J.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- Tohoku University (JP)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1995-08-29
- Volume
- 92
- Issue
- 18
- Pages
- 8453-8457
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC41175
- OpenAlex
- W2050168475
- Cited by
- 256
- References
- 0
- Citations by year
- 2026: 3 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 7 · 2019: 7 · 2018: 9 · 2017: 11 · 2016: 5 · 2015: 6 · 2014: 7 · 2013: 11 · 2012: 7
- FWCI
- 13.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (HL-20948, P01HL020948)
- National Institute of General Medical Sciences (GM-08014, T32GM008014)
- Topics
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- VLDLR, fertility, serum lipoproteins, cholesterol, triglycerides, VLDL clearance, ovulation, adipose tissue mass, body weight, LDL receptor family, female sterility, vitellogenin uptake, high-fat diet
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Female, Fertility, Homozygote, Humans, Lipoproteins, VLDL, Male, Molecular Sequence Data, Receptors, LDL, DNA Primers, Mice, Knockout, Mice
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