Overview

Also Known As:HOP-

Homozygous knock-out/reporter mice exhibit altered serum response factor and express lacZ in a pattern corresponding to that of the endogenous Hopx gene with cardiac expression especially prominent.

Donating Investigator

Rhonda Bassel-Duby, University of Texas Southwestern

Genetic overview

Genetic Background	Generation

Hopx^tm1Eno

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Hopx	HOP homeobox

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Research Applications

Research Tools
Cardiovascular Research
Developmental Biology Research
Internal/Organ Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Homozygous mice are viable and fertile on this mixed genetic background. Absence of the targeted protein is confirmed in heart and brain tissues from homozygotes. The lacZ expression pattern is similar to that of the endogenous gene. Homozygous heart tissues show altered serum response factor (SRF)-associated gene expression. Mice homozygous for this null allele segregate into two phenotypic classes characterized by an excess or deficiency of cardiac myocytes. These mutant mice may be useful in studying cardiac growth and development.

Development

A targeting vector was designed to replace the entire coding region of the targeted gene with a nuclear lacZ (nLacZ) and neomycin cassette in-frame with the endogenous initiation codon. The construct was electroporated into 129S6/SvEvTac-derived SM1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. Chimeric animals were crossed with C57BL/6J. Heterozygotes were intercrossed to homozygosity, and then bred as such for many generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred at least one generation to C57BL/6J to establish the colony.

Expression Data

Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	The lacZ expression pattern is similar to that of the endogenous Hopx gene. Highest levels of lacZ staining within cardiomyocyte nuclei in the trabecular zone. lacZ staining was also observed within the neural tube.

Control Suggestions

Approximate Controls

Additional Information

Considerations for Choosing Controls

Selected References

Shin CH; Liu ZP; Passier R; Zhang CL; Wang DZ; Harris TM; Yamagishi H; Richardson JA; Childs G; Olson EN. 2002. Modulation of cardiac growth and development by HOP, an unusual homeodomain protein. Cell 110(6):725-35PubMed: 12297046 MGI: J:79152

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Genetics

Hopx^tm1Eno

Allele Symbol: Hopx^tm1Eno

Allele Name	targeted mutation 1, Eric N Olson
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	HOP^-
Gene Symbol and Name	Hopx, HOP homeobox
Gene Synonym(s)
Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	The lacZ expression pattern is similar to that of the endogenous Hopx gene. Highest levels of lacZ staining within cardiomyocyte nuclei in the trabecular zone. lacZ staining was also observed within the neural tube.
Strain of Origin	129S6/SvEvTac
Chromosome	5
Molecular Note	The entire coding region was replaced with a cassette containing a nuclear-localized lacZ and neo. Transcript was undetected by Northern blot and RT-PCR analyses of heart and liver tissues from homozygous mutant mice. Western blot analysis confirmed the absence of normal protein in heart and brain tissues. The expression pattern of beta-galactosidase was similar to that of the endogenous gene.
Mutations Made By	Eric Olson, University of Texas Southwestern Medical

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Research Tools
- lacZ Expression
- Internal/Organ Research
- Developmental Biology Research
- Cardiovascular Research
Cardiovascular Research
- Other
- Heart Abnormalities
  - cardiomyopathy
Developmental Biology Research
- Internal/Organ Defects
  - heart
Internal/Organ Research
- Heart Abnormalities

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Hopx^tm1Eno/Hopx^tm1Eno
involves: 129S6/SvEvTac

cardiovascular system phenotype

abnormal cardiovascular system physiology

heart hyperplasia
- postnatal cardiac hypercellularity is in stark contrast to the hypocellular cardiac phenotype of embryos that die at E11.5, suggesting a finely tuned mechanism that governs the balance between cardiomyocyte proliferation and differentiation
- at P1 and P28, viable homozygotes of an isogenic or mixed genetic background exhibit a ~30% increase in the number of cardiac myocytes; however, no cardiomyocyte hypertrophy is noted up to 4 weeks of age

cardiac fibrosis
- at 6 months of age, mutant hearts with cardiomyocyte hypertrophy exhibit severe dilation and fibrosis

thick ventricular wall
- at P1, viable homozygotes display increased ventricular wall thickness relative to wild-type mice

hemopericardium
- on an isogenic 129/Sv background, ~10% of E11.5 homozygotes exhibit pericardial hemorrhaging

enlarged heart

decreased cardiac muscle contractility
- at 6 months of age, those homozygotes with hypertrophic hearts display impaired cardiac contractility or cardiac dysfunction

increased heart weight
- at P1-P28, viable homozygotes exhibit a ~20% increase in heart weight/body weight ratio relative to wild-type mice; increase difference persists through adulthood

abnormal fetal cardiomyocyte proliferation
- however, delayed withdrawal of mutant cardiomyocytes from the cell cycle is transient, as no phospho-H3-positive cardiomyocytes are detected at 4 weeks of age
- at P1, >66% of viable homozygotes exhibit prolonged cardiomyocyte proliferation, as shown by a 19-fold increase in the number of cells staining positive for the mitotic marker phospho-histone H3

cardiac hypertrophy
- at 6 months of age, a subset of viable homozygotes develop late-onset hypertrophy of cardiac myocytes

thin myocardium
- on an isogenic 129/Sv background, ~10% of E11.5 homozygotes display a hypocellular, thin-walled ventricular myocardium with numerous ruptures throughout the ventricular walls

cellular phenotype

abnormal fetal cardiomyocyte proliferation
- however, delayed withdrawal of mutant cardiomyocytes from the cell cycle is transient, as no phospho-H3-positive cardiomyocytes are detected at 4 weeks of age
- at P1, >66% of viable homozygotes exhibit prolonged cardiomyocyte proliferation, as shown by a 19-fold increase in the number of cells staining positive for the mitotic marker phospho-histone H3

embryo phenotype

embryonic growth arrest
- on an isogenic 129/Sv background, ~10% of homozygotes display a developmental arrest at E11.5

growth/size/body region phenotype

increased heart weight
- at P1-P28, viable homozygotes exhibit a ~20% increase in heart weight/body weight ratio relative to wild-type mice; increase difference persists through adulthood

enlarged heart

heart hyperplasia
- at P1 and P28, viable homozygotes of an isogenic or mixed genetic background exhibit a ~30% increase in the number of cardiac myocytes; however, no cardiomyocyte hypertrophy is noted up to 4 weeks of age
- postnatal cardiac hypercellularity is in stark contrast to the hypocellular cardiac phenotype of embryos that die at E11.5, suggesting a finely tuned mechanism that governs the balance between cardiomyocyte proliferation and differentiation

cardiac hypertrophy
- at 6 months of age, a subset of viable homozygotes develop late-onset hypertrophy of cardiac myocytes

homeostasis/metabolism phenotype

hemopericardium
- on an isogenic 129/Sv background, ~10% of E11.5 homozygotes exhibit pericardial hemorrhaging

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance
- on an isogenic 129/Sv background, ~10% of homozygotes die at E11.5 from cardiac insufficiency; as a result, viable homozygotes represent only 17% of offspring at P10
- Background Sensitivity - on a mixed 129Sv x C57BL/6J genetic background, most homozygotes are viable and represent 23% of heterozygous offspring at P10, closely approximating the expected Mendelian ratio

muscle phenotype

abnormal muscle physiology

abnormal fetal cardiomyocyte proliferation
- however, delayed withdrawal of mutant cardiomyocytes from the cell cycle is transient, as no phospho-H3-positive cardiomyocytes are detected at 4 weeks of age
- at P1, >66% of viable homozygotes exhibit prolonged cardiomyocyte proliferation, as shown by a 19-fold increase in the number of cells staining positive for the mitotic marker phospho-histone H3

decreased cardiac muscle contractility
- at 6 months of age, those homozygotes with hypertrophic hearts display impaired cardiac contractility or cardiac dysfunction

thin myocardium
- on an isogenic 129/Sv background, ~10% of E11.5 homozygotes display a hypocellular, thin-walled ventricular myocardium with numerous ruptures throughout the ventricular walls

References

Shin CH; Liu ZP; Passier R; Zhang CL; Wang DZ; Harris TM; Yamagishi H; Richardson JA; Childs G; Olson EN. 2002. Modulation of cardiac growth and development by HOP, an unusual homeodomain protein. Cell 110(6):725-35PubMed: 12297046 MGI: J:79152

Additional - Hopx^tm1Eno related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Hopx
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony on this mixed B6;129S genetic background, homozygous mice are bred.
- Additional Breeding and Husbandry Support
Citation
When using the HOP- mouse strain in a publication, please cite the originating article(s) and include JAX stock #006470 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
> >	Heterozygous for Hopx<tm1Eno>

Related Products and Services

Frozen Mouse Embryo	B6;129S-Hopx<tm1Eno>/J	$2595.00
Frozen Mouse Embryo	B6;129S-Hopx<tm1Eno>/J	$2595.00
Frozen Mouse Embryo	B6;129S-Hopx<tm1Eno>/J	$3373.50
Frozen Mouse Embryo	B6;129S-Hopx<tm1Eno>/J	$3373.50

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Additional Use Restrictions Apply

Use of MICE by companies or for-profit entities requires a license prior to shipping.

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

Also Known As:HOP-

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Hopxtm1Eno

Allele Symbol: Hopxtm1Eno

Disease Terms

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Hopxtm1Eno/Hopxtm1Enoinvolves: 129S6/SvEvTac

cardiovascular system phenotype

cellular phenotype

embryo phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

mortality/aging

muscle phenotype

References

Additional - Hopxtm1Eno related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Additional Use Restrictions Apply

Licensing Information

Hopx^tm1Eno

Allele Symbol: Hopx^tm1Eno

Genotype: Hopx^tm1Eno/Hopx^tm1Eno
involves: 129S6/SvEvTac

Additional - Hopx^tm1Eno related