ArticleProceedings of the National Academy of Sciences of the United States of America2005
Hereditary persistence of alpha-fetoprotein and H19 expression in liver of BALB/cJ mice is due to a retrovirus insertion in the Zhx2 gene.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 114 citations in OpenAlex.
- ZHX2 Alleviates Vascular Remodeling and Smooth Muscle Cell Proliferation by Transcriptional Regulation of GADD45G.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Hereditary Persistence of Alpha-Fetoprotein and Safe Application of Growth Hormone in Familial Short Stature: A Case Report.The American journal of case reports · 2025Article
- Validation studies and multiomics analysis of Zhx2 as a candidate quantitative trait gene underlying brain oxycodone metabolite (oxymorphone) levels and behavior.The Journal of pharmacology and experimental therapeutics · 2025Article
- Aquaporin 9 downregulation in KRASScientific reports · 2025Article
- ZHX2 inhibits diabetes-induced liver injury and ferroptosis by epigenetic silence of YTHDF2.Nutrition & diabetes · 2025Article
- Article
- A natural loss-of-function deletion of the cytohesin 1 (Cyth1) gene in BALB/cByJ mice does not impact cardiomyocyte polyploidy.Scientific reports · 2024Article
- Elongation of very long chain fatty acids-3 (American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- "Idiopathic" minimal change nephrotic syndrome: a podocyte mystery nears the end.American journal of physiology. Renal physiology · 2023Review
- ZHX2 emerges as a negative regulator of mitochondrial oxidative phosphorylation during acute liver injury.Nature communications · 2023Article
- ZHX2 deficiency enriches hybrid MET cells through regulating E-cadherin expression.Cell death & disease · 2023Article
- Decreased zinc-fingers and homeoboxes family expression was associated with unfavorable outcomes and immune infiltration in lung adenocarcinoma.Translational cancer research · 2023Article
- Cytokine storm-based mechanisms for extrapulmonary manifestations of SARS-CoV-2 infection.JCI insight · 2023Article
- Mitochondrial dysfunction reactivates α-fetoprotein expression that drives copper-dependent immunosuppression in mitochondrial disease models.The Journal of clinical investigation · 2023Article
- Zinc fingers and homeoboxes 2 is required for diethylnitrosamine-induced liver tumor formation in C57BL/6 mice.Hepatology communications · 2022Article
- Zinc Fingers and Homeobox Family in Cancer: A Double-Edged Sword.International journal of molecular sciences · 2022Review
- Zhx2 Is a Candidate Gene Underlying Oxymorphone Metabolite Brain Concentration Associated with State-Dependent Oxycodone Reward.The Journal of pharmacology and experimental therapeutics · 2022Article
- ZHX2 inhibits thyroid cancer metastasis through transcriptional inhibition of S100A14.Cancer cell international · 2022Article
- ZHX2 in health and disease.Frontiers in oncology · 2022Review
- Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
The alpha-fetoprotein (AFP) and H19 genes are transcribed at high levels in the mammalian fetal liver but are rapidly repressed postnatally. This repression in the liver is controlled, at least in part, by the Afr1 gene. Afr1 was defined >25 years ago when BALB/cJ mice were found to have 5- to 20-fold higher adult serum AFP levels compared with all other mouse strains; subsequent studies showed that this elevation was due to higher Afp expression in the liver. H19, which has become a model for genomic imprinting, was identified initially in a screen for Afr1-regulated genes. The BALB/cJ allele (Afr1(b)) is recessive to the wild-type allele (Afr1(a)), consistent with the idea that Afr1 functions as a repressor. By high-resolution mapping, we identified a gene that maps to the Afr1 interval on chromosome 15 and encodes a putative zinc fingers and homeoboxes (ZHX) protein. In BALB/cJ mice, this gene contains a murine endogenous retrovirus within its first intron and produces predominantly an aberrant transcript that no longer encodes a functional protein. Liver-specific overexpression of a Zhx2 transgene restores wild-type H19 repression on a BALB/cJ background, confirming that this gene is responsible for hereditary persistence of Afp and H19 in the livers of BALB/cJ mice. Thus we have identified a genetically defined transcription factor that is involved in developmental gene silencing in mammals. We present a model to explain the liver-specific phenotype in BALB/cJ mice, even though Afr1 is a ubiquitously expressed gene.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.