Fig 1.
Embryonic lethality of homozygous knockout mice of Pgam1.
(A) Summary of Pgam1 genotypes for 155 progenies from crosses between Pgam1+/− mice. +/+; wild-type, +/−; heterozygous KO, −/−; homozygous KO. (B) Summary of Pgam1 genotypes for embryo from crossing between Pgam1+/− mice at embryonic day 13.5 (E13.5). (C) Schematic diagram of glycolytic pathway. (+) indicates embryonic lethality in homozygous knockout mice, as reported previously (ref. [21–25]).
Fig 2.
Heterozygous Pgam1 knockout mice were viable.
(A) Pgam1+/− mice are viable. Representative images of wild-type and Pgam1+/− mice at 35 weeks (left panel). Genomic PCR in indicated mice was performed to verify the wild-type or deleted alleles for Pgam1 (right panels). (B and C) Assessment of PGAM expression levels and enzymatic activity in various tissues from wild-type (n = 5) and Pgam1+/− mice (n = 5) at 35 weeks. (B) Pgam1+/− mice displayed approximately 50% reduction for Pgam1 mRNA levels, compared to those from wild-type mice (upper panel), while Pgam2 mRNA levels did not show significant difference (lower panel). (C) The PGAM activity were measured in indicated tissues. Each data is shown as relative values against those in control. +/+; wild-type, +/-; heterozygous knockout.
Fig 3.
Characterization of Pgam1 heterozygous KO mice.
(A) The comparison of glycolytic mRNAs profiles between wild-type and Pgam1+/− mice. The extracts from indicated tissues were tested. (B) Intraperitoneal glucose test (IPGTT) was performed in wild-type (n = 5) and Pgam1+/− mice (n = 4). (C-E) Several physiological parameters in wild-type (n = 5) and Pgam1+/− mice (n = 5). (C) Body weight were measured every week for 30 weeks. (D) Measurements of muscle mass and visceral-fat mass by computerized tomography at 35 weeks. (E) Total cholesterol (T-Cho), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), Total protein, (TP), albumin (ALB) and blood glucose (Glu) were determined in the blood plasma of 35 weeks mice. +/+; wild-type, +/-; heterozygous knockout. Data represent the mean ± SEM. Single-asterisks (*) and double-asterisk (**) indicate statistical significance of p<0.05 and p<0.005, respectively, Student’s t-test.
Fig 4.
Glycolytic profiles in PGAM2-Tg mice.
(A) Intraperitoneal glucose test (IPGTT) was performed in control (wild-type) (n = 10) and Pgam2-Tg mice (n = 8) (Left panel). Body weight was measured at 18 weeks (Right panel). (B and C) High-fat diet (HFD) protocol was performed to induce obesity in control (n = 9) and Pgam2-Tg mice (n = 7). (B) Body weight was monitored during the protocol (left panel). (C) IPGTT was performed in HFD-fed obese mice at 18 weeks (right panel). Data represent the mean ± SEM.