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

Publication date: Available online 20 August 2019Source: Molecular and Cellular EndocrinologyAuthor(s): Kristen P. Tolson, Nuha Marooki, Andrew Wolfe, Jeremy T. Smith, Alexander S. KauffmanAbstractKisspeptin and its receptor, Kiss1r, act in 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 VO2 and VCO2, likely underlying their obesity. These findings support that our previous results in gene trap Kiss1r KOs are due to ...
Source: Molecular and Cellular Endocrinology - Category: Endocrinology Source Type: research