PUBLICATION

Bloom syndrome helicase contributes to germ line development and longevity in zebrafish

Authors

Annus, T., Müller, D., Jezsó, B., Ullaga, G., Németh, B., Harami, G.M., Orbán, L., Kovács, M., Varga, M.

ID

ZDB-PUB-220420-2

Date

2022

Source

Cell Death & Disease 13: 363 (Journal)

Registered Authors

Varga, Máté

Keywords

none

MeSH Terms

Animals
Bloom Syndrome*/genetics
Germ Cells/metabolism
Longevity/genetics
RecQ Helicases/genetics
RecQ Helicases/metabolism
Zebrafish/genetics
Zebrafish/metabolism

(all 8)

PubMed

35436990 Full text @ Cell Death Dis.

Abstract

RecQ helicases-also known as the "guardians of the genome"-play crucial roles in genome integrity maintenance through their involvement in various DNA metabolic pathways. Aside from being conserved from bacteria to vertebrates, their importance is also reflected in the fact that in humans impaired function of multiple RecQ helicase orthologs are known to cause severe sets of problems, including Bloom, Werner, or Rothmund-Thomson syndromes. Our aim was to create and characterize a zebrafish (Danio rerio) disease model for Bloom syndrome, a recessive autosomal disorder. In humans, this syndrome is characterized by short stature, skin rashes, reduced fertility, increased risk of carcinogenesis, and shortened life expectancy brought on by genomic instability. We show that zebrafish blm mutants recapitulate major hallmarks of the human disease, such as shortened lifespan and reduced fertility. Moreover, similarly to other factors involved in DNA repair, some functions of zebrafish Blm bear additional importance in germ line development, and consequently in sex differentiation. Unlike fanc genes and rad51, however, blm appears to affect its function independent of tp53. Therefore, our model will be a valuable tool for further understanding the developmental and molecular attributes of this rare disease, along with providing novel insights into the role of genome maintenance proteins in somatic DNA repair and fertility.

Genes / Markers

Marker	Marker Type	Name
blm	GENE	BLM RecQ like helicase
ddx4	GENE	DEAD (Asp-Glu-Ala-Asp) box polypeptide 4
recql	GENE	RecQ helicase-like
recql4	GENE	RecQ helicase-like 4
recql5	GENE	RecQ helicase-like 5
tp53	GENE	tumor protein p53
wrn	GENE	WRN RecQ like helicase

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Figures

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Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
blm	AB	standard conditions	Prim-5	eye	ISH	Fig. 1
blm	AB	standard conditions	14-19 somites	head	ISH	Fig. 1
blm	AB	standard conditions	Prim-5	head	ISH	Fig. 1
blm	AB	standard conditions	14-19 somites	trunk	ISH	Fig. 1
EGFP	blm^elu10/elu10; zf45Tg (AB)	standard conditions	Days 30-44	germ line cell	IFL	Fig. 3
EGFP	blm^elu10/+; zf45Tg (AB)	standard conditions	Days 30-44	germ line cell	IFL	Fig. 3
EGFP	zf45Tg (AB)	standard conditions	Days 30-44	germ line cell	IFL	Fig. 3

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
AB	chemical treatment by environment: diepoxybutane	Protruding-mouth	whole organism ab7-h2afx labeling increased distribution, abnormal	Fig. 2
AB	chemical treatment by environment: diepoxybutane	Protruding-mouth	whole organism DNA double-strand break processing increased process quality, abnormal	Fig. 2
AB	chemical treatment by environment: diepoxybutane	Protruding-mouth	whole organism morphology, abnormal	Fig. 2
AB	gamma ray	Protruding-mouth	whole organism morphology, abnormal	Fig. 2
blm^elu10/+ (AB)	standard conditions	Adult	female organism present, normal	Fig. 3
blm^elu10/+ (AB)	standard conditions	Adult	male organism normal male fertility, normal	Fig. 3
blm^elu10/+ (AB)	standard conditions	Adult	whole organism normal life span, normal	Fig. 2
blm^elu10/+ (AB)	standard conditions	Adult	whole organism viability, normal	Fig. 2
blm^elu10/+ (AB)	chemical treatment by environment: diepoxybutane	Protruding-mouth	whole organism ab7-h2afx labeling increased distribution, abnormal	Fig. 2
blm^elu10/+ (AB)	chemical treatment by environment: diepoxybutane	Protruding-mouth	whole organism morphology, abnormal	Fig. 2

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
elu10		Indel	blm
zdf1		Point Mutation	tp53
zf45Tg	Tg(ddx4:ddx4-EGFP)	Transgenic Insertion

Human Disease / Model

Human Disease	Fish	Conditions	Evidence
Bloom syndrome			TAS

Sequence Targeting Reagents

Target	Reagent	Reagent Type
blm	CRISPR1-blm	CRISPR

Fish

Fish
AB
blm^elu10/elu10 (AB)
blm^elu10/elu10; zf45Tg (AB)
blm^elu10/+ (AB)
blm^elu10/+; zf45Tg (AB)
tp53^zdf1/+ (AB)
tp53^zdf1/+; blm^elu10/elu10 (AB)
tp53^zdf1/+; blm^elu10/+ (AB)
tp53^zdf1/zdf1 (AB)
tp53^zdf1/zdf1; blm^elu10/elu10 (AB)

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Antibodies

Name	Type	Isotypes	Host Organism
Ab3-sycp3	polyclonal	IgG	Rabbit
Ab5-casp3	polyclonal		Rabbit
Ab7-h2afx	polyclonal	IgG	Rabbit

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Annus et al., 2022 ZDB-PUB-220420-2 PMID:35436990

Bloom syndrome helicase contributes to germ line development and longevity in zebrafish

Annus et al., 2022

ZDB-PUB-220420-2
PMID:35436990