The Molecular Basis of the Obese Mutation in ob2JMice
Abstract
The recessive ob2J mutation in mice results in an obese phenotype that is identical to that of the original ob allele. Initial studies indicated that ob2J mice fail to synthesize ob RNA in adipose tissue. Here we report the genomic organization of the mouse obese gene and establish the molecular genetic basis of the ob2J mutation. The ob2J mutation is the result of the insertion of a retroviral-like tranposon in the first intron of the ob gene. The insertion is a member of the ETn family of transposons and contains several splice acceptor and polyadenylation sites. This leads to the production of chimeric RNAs in which the ob first exon is spliced to sequences in the ETn insertion. As a consequence mature ob RNA is not synthesized, and leptin, the encoded protein, is not produced.
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The gene is disrupted in the 2 available alleles of ob; in the original C57/Bl6J ob/ob mutation, a nonsense mutation disrupts protein function, whereas in the second coisogenic ob 2j mutation, a retroviral insertion abrogrates expression of the coding sequence altogether.
“The gene is disrupted in the 2 available alleles of ob; in the original C57/Bl6J ob/ob mutation, a nonsense mutation disrupts protein function, whereas in the second coisogenic ob 2j mutation, a retroviral insertion abrogrates expression of the coding sequence altogether (2,21).”
From Leptin at 14 y of age: an ongoing story (2009) · cites this paper as [21]
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Leptin and the regulation of body weight in mammals
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- Authors
- Moon, B. C., & Friedman, J. M.
- Affiliations
- Howard Hughes Medical Institute (US)
- ORCID
- Friedman, Jeffrey M.
- Venue
- Genomics
- Publisher
- Elsevier BV
- Published
- 1997-05
- Volume
- 42
- Issue
- 1
- Pages
- 152-156
- ISSN
- 0888-7543 (ISSN-L)
- OpenAlex
- W1964357455
- Cited by
- 70
- References
- 14
- Citations by year
- 2023: 1 · 2020: 2 · 2019: 1 · 2018: 5 · 2016: 4 · 2015: 1 · 2014: 5 · 2013: 1 · 2012: 2
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Genomics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-41096, R01DK041096)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- obese gene, leptin, transposon insertion, introns, chimeric RNA, alternative splicing, adipose tissue, obesity, mouse genetics
- MeSH terms
- Adipose Tissue, Animals, Base Sequence, Chromosome Mapping, DNA, Genes, Recessive, Mice, Obese, Molecular Biology, Molecular Sequence Data, Mutation, Obesity, Phenotype, RNA, Gene Expression, Polymerase Chain Reaction, DNA Primers, Retroelements, Mice
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