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Human obese gene: molecular screening in Japanese and Asian Indian NIDDM patients associated with obesity
1Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Abstract:
The mouse obese (ob) gene has recently been isolated through the positional cloning technique and has been proved to result in the obese and NIDDM phenotype in mice when mutated (Nature 372:425-432, 1994). More recently, it has been demonstrated, by experiments with recombinant ob protein, that ob gene product can cause mice, including ob/ob mice, diet-induced obesity mice, and normal mice, to lower their food intake and body weight (Science 269:540-549, 1995). To investigate the genetic and/or environmental influences underlying the development of NIDDM associated with obesity, we isolated and partially sequenced the human obese (OB) gene. The human OB gene isolated in this study encoded 167 amino acids and its open reading frame was revealed to be divided into two parts with an intermediate intron of approximately 2.4 kb. Using the single-strand conformation polymorphism (SSCP) technique, we screened Japanese and Asian Indian subjects for mutations in the protein coding regions of the OB gene. A total of 75 NIDDM patients with obesity (54 Japanese and 21 Asian Indians), 40 NIDDM patients without obesity (34 Japanese and 6 Asian Indians), and 34 Japanese patients with simple obesity showed no abnormal SSCP patterns in either component of the coding sequences. These results suggested that mutations in the coding regions of the OB gene are not likely to be commonly identifiable and that there would likely be a kind of obesity-associated NIDDM not caused by mutations of the OB gene.
Insights
Mutations in the coding regions of the human obese (OB) gene are unlikely to be a common cause of obesity-associated non-insulin-dependent diabetes mellitus (NIDDM). Further research is needed to understand the genetic factors contributing to this condition.
Area of Science:
- Genetics
- Metabolic Disorders
- Molecular Biology
Background:
- The mouse obese (ob) gene mutation leads to obesity and NIDDM.
- Recombinant ob protein reduces food intake and body weight in mice.
- Understanding genetic factors in obesity-associated NIDDM is crucial.
Purpose of the Study:
- To investigate genetic and environmental influences on NIDDM associated with obesity.
- To isolate and partially sequence the human obese (OB) gene.
- To screen for mutations in the protein coding regions of the human OB gene.
Main Methods:
- Isolation and partial sequencing of the human OB gene.
- Single-strand conformation polymorphism (SSCP) technique for mutation screening.
- Analysis of Japanese and Asian Indian subjects with and without NIDDM and obesity.
Main Results:
- The human OB gene encodes 167 amino acids with a 2.4 kb intron.
- No abnormal SSCP patterns were found in the coding regions of the OB gene across all patient groups.
- This suggests mutations in OB gene coding regions are not a frequent cause of obesity-associated NIDDM.
Conclusions:
- Mutations in the coding regions of the human OB gene are not commonly identifiable in obesity-associated NIDDM.
- Obesity-associated NIDDM may develop through mechanisms other than OB gene mutations.
- Further investigation into the genetic basis of obesity-associated NIDDM is warranted.