Selecting the appropriate anesthetic protocol for the individual animal is an essential
part of laboratory animal experimentation. The present study compared the characteristics
of four anesthetic protocols in mice, focusing on the vital signs. Thirty-two male ddY
mice were divided into four groups and administered anesthesia as follows: pentobarbital
sodium monoanaesthesia; ketamine and xylazine combined (K/X); medetomidine, midazolam, and
butorphanol combined (M/M/B); and isoflurane. In each group, rectal temperature, heart
rate, respiratory rate, and O2 saturation (SPO2) were measured, and
the changes over time and instability in these signs were compared. The anesthetic depth
was also evaluated in each mouse, and the percentage of mice achieving surgical anesthesia
was calculated. K/X anesthesia caused remarkable bradycardia, while the respiratory rate
and SPO2 were higher than with the others, suggesting a relatively strong
cardiac influence and less respiratory depression. The M/M/B group showed a relatively
lower heart rate and SPO2, but these abnormalities were rapidly reversed by
atipamezole administration. The pentobarbital group showed a lower SPO2, and
62.5% of mice did not reach a surgical anesthetic depth. The isoflurane group showed a
marked decrease in respiratory rate compared with the injectable anesthetic groups.
However, it had the most stable SPO2 among the groups, suggesting a higher
tidal volume. The isoflurane group also showed the highest heart rate during anesthesia.
In conclusion, the present study showed the cardiorespiratory characteristics of various
anesthetic protocols, providing basic information for selecting an appropriate anesthetic
for individual animals during experimentation.
TET2 enzymatically converts 5-methylcytosine to 5-hydroxymethylcytosine as well as other covalently-modified cytosines and its mutations are common in myeloid leukemia. However, the exact mechanism and the extent to which TET2 mutations affect DNA methylation remain in question. Here we report on DNA methylomes in TET2 wild type (TET2-WT) and mutant (TET2-MT) cases of chronic myelomonocytic leukemia (CMML). We analyzed 85,134 CpG sites (28,114 sites in CpG islands (CGIs) and 57,020 in non-CpG islands (NCGIs)). TET2 mutations do not explain genome-wide differences in DNA methylation in CMML, and we found few and inconsistent differences at CGIs between TET2-WT and TET2-MT cases. By contrast, we identified 409 (0.71%) TET2-specific differentially methylated CpGs (tet2-DMCs) in NCGIs, 86% of which were hypermethylated in TET2-MT cases, suggesting a strikingly different biology of the effects of TET2 mutations at CGIs and NCGIs. DNA methylation of tet2-DMCs at promoters and non-promoters repressed gene expression. Tet2-DMCs showed significant enrichment at hematopoietic-specific enhancers marked by H3K4me1, and at binding sites for the transcription factor p300. Tet2-DMCs showed significantly lower 5-hydroxymethylcytosine in TET2-MT cases. We conclude that leukemia-associated TET2 mutations affect DNA methylation at NCGI regions containing hematopoietic-specific enhancers and transcription factor binding sites.
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