NCBI Logo
GEO Logo
   NCBI > GEO > Accession DisplayHelp Not logged in | LoginHelp
GEO help: Mouse over screen elements for information.
          Go
Series GSE154156 Query DataSets for GSE154156
Status Public on Mar 31, 2021
Title The Intrinsic Activity of Thyroxine is Critical for Survival and Growth and Regulates Gene expression in Neonatal Liver
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Background: Thyroxine (T4) is generally considered to be a pro-hormone that requires conversion to 3,5,3’-triiodothyronine (T3) to exert biological activity. Although evidence suggests that T4 has intrinsic activity, it is questionable if this activity has any physiological relevance. Methods: To answer this question, triple KO mice (Triples) that cannot express the types 1 (D1) and 2 (D2) deiodinase and the Pax8 genes were generated. Thus they lack a thyroid and cannot convert T4 to T3. Triples were injected on alternate days with either vehicle or physiological doses of T4, T3 or T3+T4 from postnatal days 2 to 14. They were euthanized at P15 and RNA-seq was employed to profile gene expression in liver. In another experiment, Pax8KO mice were injected with T3, T4 or T4 +T3, and growth rate and survival to P84 were determined. Results: The growth retardation of Triples was not improved by either T3 or T4 alone but was significantly improved by T4+T3. In liver, T4 significantly regulated the expression of genes that were also regulated by T3, but the proportion of genes that were negatively regulated was higher in mice treated with T4 than with T3. Treatment with T4+T3 identified genes that were regulated synergistically by T3 and T4, and genes that were regulated only by T4+T3. Analysis of these genes revealed enrichment in mechanisms related to cell proliferation and cholesterol physiology, suggesting a unique contribution of T4 to these biological functions. Pax8KO mice all survived to P84 when injected with T4 or T4+T3 but survival rate with T3 was 50% and 10% at 3.5 and 12 weeks of life, respectively. Conclusion: T4 has intrinsic activity in vivo and is critical for survival and growth. At a physiological level, T4 per se can up- or down-regulate many T3 target genes in the neonatal liver. While most of these genes are also regulated by T3, subsets respond exclusively to T4 or demonstrate enhanced or normalized expression only in the presence of both hormones. These studies demonstrate for the first time a complex dependency on both T4 and T3 for normal mammalian growth and development.
 
Overall design newborn mice lacking a thyroid and type 1 and type 2 deiodinases as well as littermate controls with a thyroid were injected with vehicle, T3, T4 or T3+T4 for two weeks
 
Contributor(s) Galton VA, Martinez ME, Dragon JA, St Germain DL, Hernandez A
Citation(s) 32791885
Submission date Jul 09, 2020
Last update date Mar 31, 2021
Contact name Valerie Anne Galton
E-mail(s) val.galton@dartmouth.edu
Organization name Dartmouth Geisel School of Medicine
Department Physiology and Neurobiology
Street address 1 Medical Center Drive
City Lebanon
State/province New Hampshire
ZIP/Postal code 03756
Country USA
 
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (31)
GSM4665155 vagalton#42_Cont
GSM4665156 vagalton#47_Cont
GSM4665157 vagalton_#49_Cont
Relations
BioProject PRJNA645240
SRA SRP271186

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE154156_byGeneAnnotationcounts.csv.gz 1.8 Mb (ftp)(http) CSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

| NLM | NIH | GEO Help | Disclaimer | Accessibility |
NCBI Home NCBI Search NCBI SiteMap