PUBLICATION

A missense mutation in zbtb17 blocks the earliest steps of T cell differentiation in zebrafish

Authors

Lawir, D.F., Iwanami, N., Schorpp, M., Boehm, T.

ID

ZDB-PUB-170308-8

Date

2017

Source

Scientific Reports 7: 44145 (Journal)

Registered Authors

Boehm, Tom, Schorpp, Michael

Keywords

Haematopoiesis, Immunology, Lymphopoiesis

MeSH Terms

T-Lymphocytes/cytology
T-Lymphocytes/immunology*
Transcription Factors*/genetics
Transcription Factors*/immunology
Zebrafish Proteins*/genetics
Zebrafish Proteins*/immunology
Mutation, Missense*
Animals
Cell Differentiation*/genetics
Cell Differentiation*/immunology
Zebrafish*/genetics
Zebrafish*/immunology

(all 12)

PubMed

28266617 Full text @ Sci. Rep.

Abstract

T cells are an evolutionarily conserved feature of the adaptive immune systems of vertebrates. Comparative studies using evolutionarily distant species hold great promise for unraveling the genetic landscape underlying this process. To this end, we used ENU mutagenesis to generate mutant zebrafish with specific aberrations in early T cell development. Here, we describe the identification of a recessive missense mutation in the transcriptional regulator zbtb17 (Q562K), which affects the ninth zinc finger module of the protein. Homozygous mutant fish exhibit an early block of intrathymic T cell development, as a result of impaired thymus colonization owing to reduced expression of the gene encoding the homing receptor ccr9a, and inefficient T cell differentiation owing to reduced expression of socs1a. Our results reveal the zbtb17-socs1 axis as an evolutionarily conserved central regulatory module of early T cell development of vertebrates.

Genes / Markers

Figures

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Expression

Gene	Fish	Conditions	Stage	Qualifier	Anatomy	Assay	Figure
ccr9a	TU + MO1-socs3b	standard conditions	Day 5		whole organism	RTPCR	Fig. 5
ccr9a	TU + MO1-zbtb17	standard conditions	Day 5		whole organism	RTPCR	Fig. 5
ccr9a	TU + MO3-socs1a	standard conditions	Day 5		whole organism	RTPCR	Fig. 5
ccr9a	WT	standard conditions	Day 5		thymus anatomical region	ISH	Fig. 5
ccr9a	zbtb17^{t20463/t20463}	standard conditions	Day 5	Not Detected	thymus anatomical region	ISH	Fig. 5
ccr9b	TU + MO1-socs3b	standard conditions	Day 5		whole organism	RTPCR	Fig. 5
ccr9b	TU + MO1-zbtb17	standard conditions	Day 5		whole organism	RTPCR	Fig. 5
ccr9b	TU + MO3-socs1a	standard conditions	Day 5		whole organism	RTPCR	Fig. 5
ccr9b	WT	standard conditions	Day 5		thymus	ISH	Fig. 5
ccr9b	zbtb17^{t20463/t20463}	standard conditions	Day 5	Not Detected	thymus	ISH	Fig. 5

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
TU + MO1-socs1b	standard conditions	Day 4	T cell differentiation decreased occurrence, abnormal	Fig. 3
TU + MO1-socs1b	standard conditions	Day 4	thymus T cell rag1 expression decreased amount, abnormal	Fig. 3
TU + MO1-socs1b	standard conditions	Day 4	whole organism rag1 expression decreased amount, abnormal	Fig. 3
TU + MO1-socs3b	standard conditions	Day 4	thymus T cell rag1 expression increased amount, abnormal	Fig. 3
TU + MO1-socs3b	standard conditions	Day 4	whole organism rag1 expression increased amount, abnormal	Fig. 3
TU + MO1-socs3b	standard conditions	Day 5	whole organism ccr9a expression increased amount, abnormal	Fig. 5
TU + MO1-socs3b	standard conditions	Day 5	whole organism rag1 expression increased amount, abnormal	Fig. 5
TU + MO1-zbtb17	standard conditions	Day 4	adenohypophysis gh1 expression decreased amount, abnormal	Fig. 2
TU + MO1-zbtb17	standard conditions	Day 4	T cell differentiation decreased occurrence, abnormal	Fig. 2
TU + MO1-zbtb17	standard conditions	Day 4	thymus T cell rag1 expression decreased amount, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
fr101Tg	TgBAC(ikzf1:EGFP)	Transgenic Insertion
t20463		Point Mutation	zbtb17

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
socs1a	MO3-socs1a	MRPHLNO
socs1b	MO1-socs1b	MRPHLNO
socs3a	MO2-socs3a	MRPHLNO
socs3b	MO1-socs3b	MRPHLNO
zbtb17	MO1-zbtb17	MRPHLNO
zbtb17	MO2-zbtb17	MRPHLNO

Fish

Fish
fr101Tg
fr101Tg + MO1-socs3b
fr101Tg + MO1-zbtb17
fr101Tg + MO3-socs1a
TU
TU + MO1-socs1b
TU + MO1-socs3b
TU + MO1-zbtb17
TU + MO2-socs3a
TU + MO2-zbtb17

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Lawir et al., 2017 ZDB-PUB-170308-8 PMID:28266617

A missense mutation in zbtb17 blocks the earliest steps of T cell differentiation in zebrafish

Lawir et al., 2017

ZDB-PUB-170308-8
PMID:28266617