دورية أكاديمية
أعرض في EDS

Cre/lox generation of a novel whole-body Kiss1r KO mouse line recapitulates a hypogonadal, obese, and metabolically-impaired phenotype.

التفاصيل البيبلوغرافية
العنوان: Cre/lox generation of a novel whole-body Kiss1r KO mouse line recapitulates a hypogonadal, obese, and metabolically-impaired phenotype.
المؤلفون: Tolson KP; Department of OBGYN and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA., Marooki N; Department of OBGYN and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA., Wolfe A; Department of Pediatrics and Physiology, Johns Hopkins University, Baltimore, MD, USA., Smith JT; School of Human Sciences, University of Western Australia, Perth, Australia., Kauffman AS; Department of OBGYN and Reproductive Sciences, University of California, San Diego, La Jolla, CA, USA. Electronic address: akauffman@ucsd.edu.
المصدر: Molecular and cellular endocrinology [Mol Cell Endocrinol] 2019 Dec 01; Vol. 498, pp. 110559. Date of Electronic Publication: 2019 Aug 20.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: North Holland Publishing Country of Publication: Ireland NLM ID: 7500844 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8057 (Electronic) Linking ISSN: 03037207 NLM ISO Abbreviation: Mol Cell Endocrinol Subsets: MEDLINE
أسماء مطبوعة: Publication: Limerick : North Holland Publishing
Original Publication: Amsterdam, North-Holland.
مواضيع طبية MeSH: Reproduction*, Glucose Intolerance/*pathology , Hypogonadism/*pathology , Integrases/*metabolism , Metabolic Diseases/*pathology , Obesity/*pathology , Receptors, Kisspeptin-1/*physiology, Adiposity ; Animals ; Body Weight ; Energy Metabolism ; Female ; Glucose Intolerance/etiology ; Glucose Intolerance/metabolism ; Hypogonadism/etiology ; Hypogonadism/metabolism ; Integrases/genetics ; Male ; Metabolic Diseases/etiology ; Metabolic Diseases/metabolism ; Mice ; Mice, Knockout ; Obesity/etiology ; Obesity/metabolism ; Phenotype ; Signal Transduction
مستخلص: Kisspeptin and its receptor, Kiss1r, act centrally to stimulate reproduction. Recent evidence indicates that kisspeptin is also important for body weight and metabolism, as whole-body Kiss1r KO mice, developed with gene trap technology, display obesity and reduced metabolism. Kiss1r is expressed in brain and multiple peripheral tissues, but it is unknown which is responsible for the metabolic phenotype. Here, we sought to confirm that 1) the metabolic phenotype of the gene trap Kiss1r KOs is due to disruption of kisspeptin signaling and not off-target effects of viral mutagenesis, and 2) the Kiss1r flox line is suitable for creating conditional KOs to study the metabolic phenotype. We used Cre/lox technology (Zp3-Cre/Kiss1r flox) to develop a new global Kiss1r KO ("Kiss1r gKO") to compare with the original gene trap KO phenotype. We confirmed that deleting exon 2 of Kiss1r from the entire body induces hypogonadism in both sexes. Moreover, global deletion of Kiss1r induced obesity in females, but not males, along with increased adiposity and impaired glucose tolerance, similar to the gene trap Kiss1r KOs. Likewise, Kiss1r gKO females had decreased VO 2 and VCO 2 , likely underlying their obesity. These findings support that our previous results in gene trap Kiss1r KOs are due to disrupted kisspeptin signaling, and further highlight a role for Kiss1r signaling in energy expenditure and metabolism besides controlling reproduction. Moreover, given Kiss1r expression in multiple cell-types, our findings indicate that the Kiss1r flox line is viable for future investigations to isolate specific target cells of kisspeptin's metabolic effects.
(Copyright © 2019 Elsevier B.V. All rights reserved.)
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معلومات مُعتمدة: T32 HD007203 United States HD NICHD NIH HHS; R01 HD090161 United States HD NICHD NIH HHS; P30 DK063491 United States DK NIDDK NIH HHS; U01 HD066432 United States HD NICHD NIH HHS; P50 HD012303 United States HD NICHD NIH HHS
فهرسة مساهمة: Keywords: Adipose; Energy expenditure; Fat; GPR54; Kiss1; Kiss1r; Kisspeptin; Metabolism; Obesity
المشرفين على المادة: 0 (Kiss1r protein, mouse)
0 (Receptors, Kisspeptin-1)
EC 2.7.7.- (Cre recombinase)
EC 2.7.7.- (Integrases)
تواريخ الأحداث: Date Created: 20190824 Date Completed: 20200624 Latest Revision: 20201201
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC6814569
DOI: 10.1016/j.mce.2019.110559
PMID: 31442544
قاعدة البيانات: MEDLINE
الوصف
تدمد:1872-8057
DOI:10.1016/j.mce.2019.110559