title: Deletion of Gpr128 results in weight loss and increased intestinal contraction frequency.
abstract: OBJECTIVE
  To generate a Gpr128 gene knockout mouse model and to investigate its phenotypes and the biological function of the Gpr128 gene.
  
  
  METHODS
  Bacterial artificial chromosome-retrieval methods were used for constructing the targeting vector. Using homologous recombination and microinjection technology, a Gpr128 knockout mouse model on a mixed 129/BL6 background was generated. The mice were genotyped by polymerase chain reaction (PCR) analysis of tail DNA and fed a standard laboratory chow diet. Animals of both sexes were used, and the phenotypes were assessed by histological, biochemical, molecular and physiological analyses. Semi-quantitative reverse transcription-PCR and Northern blotting were used to determine the tissue distribution of Gpr128 mRNA. Beginning at the age of 4 wk, body weights were recorded every 4 wk. Food, feces, blood and organ samples were collected to analyze food consumption, fecal quantity, organ weight and constituents of the blood and plasma. A Trendelenburg preparation was utilized to examine intestinal motility in wild-type (WT) and Gpr128(-/-) mice at the age of 8 and 32 wk.
  
  
  RESULTS
  Gpr128 mRNA was highly and exclusively detected in the intestinal tissues. Targeted deletion of Gpr128 in adult mice resulted in reduced body weight gain, and mutant mice exhibited an increased frequency of peristaltic contraction and slow wave potential of the small intestine. The Gpr128(+/+) mice gained more weight on average than the Gpr128(-/-) mice since 24 wk, being 30.81 ± 2.84 g and 25.74 ± 4.50 g, respectively (n = 10, P < 0.01). The frequency of small intestinal peristaltic contraction was increased in Gpr128(-/-) mice. At the age of 8 wk, the frequency of peristalsis with an intraluminal pressure of 3 cmH2O was 6.6 ± 2.3 peristalsis/15 min in Gpr128(-/-) intestine (n = 5) vs 2.6 ± 1.7 peristalsis/15 min in WT intestine (n = 5, P < 0.05). At the age of 32 wk, the frequency of peristaltic contraction with an intraluminal pressure of 2 and 3 cmH2O was 4.6 ± 2.3 and 3.1 ± 0.8 peristalsis/15 min in WT mice (n = 8), whereas in Gpr128(-/-) mice (n = 8) the frequency of contraction was 8.3 ± 3.0 and 7.4 ± 3.1 peristalsis/15 min, respectively (2 cmH2O: P < 0.05 vs WT; 3 cmH2O: P < 0.01 vs WT). The frequency of slow wave potential in Gpr128(-/-) intestine (35.8 ± 4.3, 36.4 ± 4.2 and 37.1 ± 4.8/min with an intraluminal pressure of 1, 2 and 3 cmH2O, n = 8) was also higher than in WT intestine (30.6 ± 4.2, 31.4 ± 3.9 and 31.9 ± 4.5/min, n = 8, P < 0.05).
  
  
  CONCLUSIONS
  We have generated a mouse model with a targeted deletion of Gpr128 and found reduced body weight and increased intestinal contraction frequency in this animal model.
authors.affiliation: Ying-Yin Ni, Yan Chen, Fang Wang, Xiao-Lin Wu, Su-Ying Dang, Ming-Min Gu, Zhu-Gang Wang, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Ying-Yin
authors.initials: YY
authors.lastname: Ni
authors.affiliation: Ying-Yin Ni, Yan Chen, Fang Wang, Xiao-Lin Wu, Su-Ying Dang, Ming-Min Gu, Zhu-Gang Wang, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Ying-Yin Ni, Yan Chen, Fang Wang, Xiao-Lin Wu, Su-Ying Dang, Ming-Min Gu, Zhu-Gang Wang, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Shun-Yuan
authors.initials: SY
authors.lastname: Lu
authors.affiliation: Ying-Yin Ni, Yan Chen, Fang Wang, Xiao-Lin Wu, Su-Ying Dang, Ming-Min Gu, Zhu-Gang Wang, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Bi-Ying
authors.initials: BY
authors.lastname: Sun
authors.affiliation: Ying-Yin Ni, Yan Chen, Fang Wang, Xiao-Lin Wu, Su-Ying Dang, Ming-Min Gu, Zhu-Gang Wang, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Ying-Yin Ni, Yan Chen, Fang Wang, Xiao-Lin Wu, Su-Ying Dang, Ming-Min Gu, Zhu-Gang Wang, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Xiao-Lin
authors.initials: XL
authors.lastname: Wu
authors.affiliation: Ying-Yin Ni, Yan Chen, Fang Wang, Xiao-Lin Wu, Su-Ying Dang, Ming-Min Gu, Zhu-Gang Wang, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Su-Ying
authors.initials: SY
authors.lastname: Dang
authors.affiliation: Ying-Yin Ni, Yan Chen, Fang Wang, Xiao-Lin Wu, Su-Ying Dang, Ming-Min Gu, Zhu-Gang Wang, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Zhang
authors.affiliation: Ying-Yin Ni, Yan Chen, Fang Wang, Xiao-Lin Wu, Su-Ying Dang, Ming-Min Gu, Zhu-Gang Wang, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Hong-Xin
authors.initials: HX
authors.lastname: Zhang
authors.affiliation: Ying-Yin Ni, Yan Chen, Fang Wang, Xiao-Lin Wu, Su-Ying Dang, Ming-Min Gu, Zhu-Gang Wang, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Kuang
authors.affiliation: Ying-Yin Ni, Yan Chen, Fang Wang, Xiao-Lin Wu, Su-Ying Dang, Ming-Min Gu, Zhu-Gang Wang, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Fei
authors.affiliation: Ying-Yin Ni, Yan Chen, Fang Wang, Xiao-Lin Wu, Su-Ying Dang, Ming-Min Gu, Zhu-Gang Wang, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Ming-Min
authors.initials: MM
authors.lastname: Gu
authors.affiliation: Ying-Yin Ni, Yan Chen, Fang Wang, Xiao-Lin Wu, Su-Ying Dang, Ming-Min Gu, Zhu-Gang Wang, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Wei-Fang
authors.initials: WF
authors.lastname: Rong
authors.affiliation: Ying-Yin Ni, Yan Chen, Fang Wang, Xiao-Lin Wu, Su-Ying Dang, Ming-Min Gu, Zhu-Gang Wang, Department of Medical Genetics, E-Institutes of Shanghai Universities, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Zhu-Gang
authors.initials: ZG
authors.lastname: Wang
mesh_terms: D000367:Age Factors; D000818:Animals; D005260:Female; D017353:Gene Deletion; D005786:Gene Expression Regulation; D005838:Genotype; D007583:Jejunum / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009119:Muscle Contraction / Q000235:genetics*; D010528:Peristalsis / Q000235:genetics*; D010641:Phenotype; D011312:Pressure; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency* / Q000235:genetics*; D015431:Weight Loss / Q000235:genetics*
chemical_list: C000593025:Gpr128 protein, mouse; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled
keywords: G-protein-coupled receptors; Gpr128; Intestinal contraction frequency; Knockout mouse; Weight loss