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Publication : A mutation in mouse Krüppel-like factor 15 alters the gut microbiome and response to obesogenic diet.

First Author  Svenson KL Year  2019
Journal  PLoS One Volume  14
Issue  9 Pages  e0222536
PubMed ID  31553739 Mgi Jnum  J:280739
Mgi Id  MGI:6362969 Doi  10.1371/journal.pone.0222536
Citation  Svenson KL, et al. (2019) A mutation in mouse Kruppel-like factor 15 alters the gut microbiome and response to obesogenic diet. PLoS One 14(9):e0222536
abstractText  We identified a mouse strain, HLB444, carrying an N-ethyl-N-nitrosourea (ENU)-induced mutation in a highly conserved C2H2 zinc-finger DNA binding motif of the transcriptional regulator KLF15 that exhibits resistance to diet-induced obesity. Characterization of the HLB444 mutant model on high-fat and chow diets revealed a number of phenotypic differences compared to wild-type controls. When fed a high fat diet, HLB444 had lower body fat, resistance to hepatosteatosis, lower circulating glucose and improved insulin sensitivity compared to C57BL/6J controls. Gut microbial profiles in HLB444 generated from 16S rRNA sequencing of fecal samples differed from controls under both chow and high fat diets. HLB444 shares similar phenotypic traits with engineered full- and adipose-specific Klf15 knockout strains; however, some phenotypic differences between this mutant and the other models suggest that the Klf15 mutation in HLB444 is a hypomorphic variant. The HLB444 model will inform further annotation of transcriptional functions of KLF15, especially with respect to the role of the first zinc-finger domain.
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