PUBLICATION

Inhibition of the pim1 oncogene results in diminished visual function

Authors

Yin, J., Shine, L., Raycroft, F., Deeti, S., Reynolds, A., Ackerman, K.M., Glaviano, A., O'Farrell, S., O'Leary, O., Kilty, C., Kennedy, C., McLoughlin, S., Rice, M., Russell, E., Higgins, D.G., Hyde, D.R., and Kennedy, B.N.

ID

ZDB-PUB-130118-6

Date

2012

Source

PLoS One 7(12): e52177 (Journal)

Registered Authors

Hyde, David R., Kennedy, Breandan N., McLoughlin, Sarah, Yin, Jun

Keywords

none

Datasets

GEO:GSE19320

MeSH Terms

Zebrafish/genetics
Zebrafish/growth & development
Zebrafish/metabolism*
Electroretinography
Phylogeny
Reverse Transcriptase Polymerase Chain Reaction
Animals
Zebrafish Proteins/genetics
Zebrafish Proteins/metabolism
Suppressor of Cytokine Signaling Proteins/genetics
Suppressor of Cytokine Signaling Proteins/metabolism
Vision Disorders/drug therapy
Vision Disorders/etiology*
Vision Disorders/pathology
STAT3 Transcription Factor/genetics
STAT3 Transcription Factor/metabolism
Gene Expression Regulation, Developmental*
Real-Time Polymerase Chain Reaction
RNA, Messenger/genetics
Signal Transduction/drug effects
Morpholinos/pharmacology*
Blotting, Western
Proto-Oncogene Proteins c-pim-1/antagonists & inhibitors*
Proto-Oncogene Proteins c-pim-1/genetics
Proto-Oncogene Proteins c-pim-1/metabolism
Larva/drug effects
Larva/growth & development
Larva/metabolism

(all 28)

PubMed

23300608 Full text @ PLoS One

Abstract

Our objective was to profile genetic pathways whose differential expression correlates with maturation of visual function in zebrafish. Bioinformatic analysis of transcriptomic data revealed Jak-Stat signalling as the pathway most enriched in the eye, as visual function develops. Real-time PCR, western blotting, immunohistochemistry and in situ hybridization data confirm that multiple Jak-Stat pathway genes are up-regulated in the zebrafish eye between 3–5 days post-fertilisation, times associated with significant maturation of vision. One of the most up-regulated Jak-Stat genes is the proto-oncogene Pim1 kinase, previously associated with haematological malignancies and cancer. Loss of function experiments using Pim1 morpholinos or Pim1 inhibitors result in significant diminishment of visual behaviour and function. In summary, we have identified that enhanced expression of Jak-Stat pathway genes correlates with maturation of visual function and that the Pim1 oncogene is required for normal visual function.

Genes / Markers

Figures

Show all Figures

Expression

Gene	Fish	Conditions	Stage	Anatomy	Assay	Figure
bcl2l1	WT	standard conditions	Day 5	whole organism	RTPCR	Fig. 3
bcl2l1	WT	standard conditions	Protruding-mouth	whole organism	RTPCR	Fig. 3
cisha	WT	standard conditions	Protruding-mouth	whole organism	RTPCR	Fig. 3
cisha	WT	standard conditions	Day 5	whole organism	RTPCR	Fig. 3
EGFP	nt11Tg	standard conditions	Days 7-13	lens	IFL	Fig. 5
EGFP	nt11Tg + MO3-socs1a	standard conditions	Days 7-13	lens	IFL	Fig. 5
EGFP	nt11Tg + MO3-stat3	standard conditions	Days 7-13	lens	IFL	Fig. 5
EGFP	nt11Tg + MO3-stat3 + MO5-socs3a	standard conditions	Days 7-13	lens	IFL	Fig. 5
jak1	WT	standard conditions	Protruding-mouth	whole organism	RTPCR	Fig. 3
jak1	WT	standard conditions	Day 5	whole organism	RTPCR	Fig. 3

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Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment: protein kinase inhibitor	Day 5	eye decreased size, abnormal	Fig. 8
WT	chemical treatment: protein kinase inhibitor	Day 5	hyaloid vessel decreased branchiness, abnormal	Fig. 8
WT	chemical treatment: protein kinase inhibitor	Day 5	optokinetic behavior disrupted, abnormal	Fig. 9
WT	chemical treatment: protein kinase inhibitor	Day 5	optomotor response disrupted, abnormal	Fig. 10
WT	chemical treatment: protein kinase inhibitor	Day 5	sensory perception of touch process quality, normal	Fig. 9
WT	chemical treatment: protein kinase inhibitor	Day 5	eye decreased size, abnormal	Fig. 8
WT	chemical treatment: protein kinase inhibitor	Day 5	hyaloid vessel decreased branchiness, abnormal	Fig. 8
WT	chemical treatment: protein kinase inhibitor	Day 5	optokinetic behavior disrupted, abnormal	Fig. 9
WT	chemical treatment: protein kinase inhibitor	Day 5	optomotor response disrupted, abnormal	Fig. 10
WT	chemical treatment: protein kinase inhibitor	Day 5	sensory perception of touch process quality, normal	Fig. 9

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
nt11Tg	Tg(gfap:EGFP)	Transgenic Insertion

Human Disease / Model

Sequence Targeting Reagents

Target	Reagent	Reagent Type
pim1	MO1-pim1	MRPHLNO
pim1	MO2-pim1	MRPHLNO
socs1a	MO3-socs1a	MRPHLNO
socs3a	MO5-socs3a	MRPHLNO
stat3	MO3-stat3	MRPHLNO

Fish

Fish
nt11Tg
nt11Tg + MO3-socs1a
nt11Tg + MO3-stat3
nt11Tg + MO3-stat3 + MO5-socs3a
WT
WT + MO1-pim1 + MO2-pim1
WT + MO3-socs1a
WT + MO3-stat3
WT + MO3-stat3 + MO5-socs3a

Antibodies

Name	Type	Antigen Genes	Isotypes	Host Organism
Ab1-elavl	monoclonal	elavl3 elavl4	IgG2b	Mouse
Ab1-opn1mw1	polyclonal	opn1mw1		Rabbit
Ab1-pim1	polyclonal	pim1	IgG	Rabbit
Ab1-socs1a	polyclonal	socs1a		Rabbit
Ab1-socs3a	polyclonal	socs3a		Rabbit
Ab2-rho	polyclonal	rho		Rabbit
Ab3-stat3	polyclonal	stat3		Rabbit
Ab4-pcna	polyclonal	pcna		Rabbit

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Orthology

Gene	Orthology
pim1
pim2
pim3

Engineered Foreign Genes

Marker	Marker Type	Name
EGFP	EFG	EGFP

Mapping

Yin et al., 2012 ZDB-PUB-130118-6 PMID:23300608

Inhibition of the pim1 oncogene results in diminished visual function

Yin et al., 2012

ZDB-PUB-130118-6
PMID:23300608