PUBLICATION
Transgenerational inheritance of impaired larval T cell development in zebrafish
- Authors
- Iwanami, N., Lawir, D.F., Sikora, K., O Meara, C., Takeshita, K., Schorpp, M., Boehm, T.
- ID
- ZDB-PUB-201002-6
- Date
- 2020
- Source
- Nature communications 11: 4505 (Journal)
- Registered Authors
- Boehm, Tom, Schorpp, Michael
- Keywords
- none
- Datasets
- GEO:GSE98647
- MeSH Terms
-
- Alleles
- Animals
- Animals, Genetically Modified
- Cell Differentiation/genetics*
- Core Binding Factor Alpha 3 Subunit/genetics
- DNA (Cytosine-5-)-Methyltransferase 1/genetics
- DNA (Cytosine-5-)-Methyltransferase 1/metabolism
- DNA Methylation
- Epigenesis, Genetic
- Female
- Genes, Recessive*
- Genetics
- Larva/cytology
- Larva/growth & development*
- Lymphopoiesis/genetics*
- Male
- Mutation
- Regulatory-Associated Protein of mTOR/genetics
- Spermatozoa/metabolism
- T-Lymphocytes/physiology*
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 32908148 Full text @ Nat. Commun.
Citation
Iwanami, N., Lawir, D.F., Sikora, K., O Meara, C., Takeshita, K., Schorpp, M., Boehm, T. (2020) Transgenerational inheritance of impaired larval T cell development in zebrafish. Nature communications. 11:4505.
Abstract
Evidence for transgenerational inheritance of epigenetic information in vertebrates is scarce. Aberrant patterns of DNA methylation in gametes may set the stage for transmission into future generations. Here, we describe a viable hypomorphic allele of dnmt1 in zebrafish that causes widespread demethylation of CpG dinucleotides in sperm and somatic tissues. We find that homozygous mutants are essentially normal, with the exception of drastically impaired lymphopoiesis, affecting both larval and adult phases of T cell development. The phenotype of impaired larval (but not adult) T cell development is transmitted to subsequent generations by genotypically wildtype fish. We further find that about 200 differentially methylated regions in sperm DNA of transmitting and non-transmitting males, including hypermethylated sites associated with runx3 and rptor genes, whose reduced activities are associated with impaired larval T cell development. Our results indicate a particular sensitivity of larval T cell development to transgenerationally inherited epimutations.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping