Overview

These Osr1^tm1Jian (Odd1-LacZ) mice harbor a nuclear localized β-galactosidase "knock-in" allele that also abolishes endogenous Osr1 (odd-skipped related 1 (Drosophila)) gene function. These mice may be useful as a lacZ reporter for Osr1 expression or as a knockout model for studying developmental biology (heart morphogenesis and urogenital development).

Donating Investigator

Rulang Jiang, University of Rochester

Genetic overview

Genetic Background	Generation

Osr1^tm1Jian

Allele Type	Gene Symbol	Gene Name
Targeted (Reporter, Null/Knockout)	Osr1	odd-skipped related transcription factor 1

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Research Applications

Developmental Biology Research
Internal/Organ Research
Research Tools
Cardiovascular Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The Osr1^tm1Jian (Odd1-LacZ) mutation abolishes endogenous gene function and expresses a β-galactosidase fusion protein (fused in-frame with the N-terminal 16 amino acid residues of the endogenous protein). Under control of the upstream promoter/enhancer elements, lacZ expression is directed to the same tissues as the wild-type gene (for example, β-galactosidase expression during embryogenesis is detected at E7.5 in the intermediate mesoderm, is expanded to the gut endoderm, lung bud mesenchyme and myocardial cells by E9.5, and is activated in developing branchial arches and limb buds by E10.5). Almost all (`95%) of homozygous mice die in utero between E11.5-E12.5 from circulation distress; exhibiting malformed atrial septum, dilated atria with hypoplastic venous valves, and blood backflow from the heart into systemic veins. Homozygotes also exhibit complete agenesis of adrenal glands, metanephric kidneys, gonads, and defects in pericardium formation. Heterozygotes are viable and fertile. These Odd1-mutant mice may be useful as a lacZ reporter for Osr1 expression or as a knockout model for studying developmental biology (heart morphogenesis and urogenital development).

Development

A targeting vector was designed to replace part of exon 2 of the Osr1 locus with the initial 16 codons of the Osr1 open reading frame fused in-frame with a nuclear localized β-galactosidase (lacZ) and loxP-flanked neo cassette. The construct was electroporated into 129S1/Sv-derived CJ7 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric males were bred with C57BL/6J females to establish the colony. Mice were then backcrossed to C57BL/6J for approximately 10 generations prior to arrival at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony. The Y chromosome may not have been fixed to the genetic background during the backcross.

Expression Data

Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	LacZ expression mimics that of the wild-type targeted gene. During embryogenesis is detected at E7.5 in the intermediate mesoderm, is expanded to the gut endoderm, lung bud mesenchyme and myocardial cells by E9.5, and is activated in developing branchial arches and limb buds by E10.5.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Wang Q; Lan Y; Cho ES; Maltby KM; Jiang R. 2005. Odd-skipped related 1 (Odd 1) is an essential regulator of heart and urogenital development. Dev Biol 288(2):582-94PubMed: 16223478 MGI: J:104942

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Genetics

Osr1^tm1Jian

Allele Symbol: Osr1^tm1Jian

Allele Name	targeted mutation 1, Rulang Jiang
Allele Type	Targeted (Reporter, Null/Knockout)
Allele Synonym(s)	Odd1^-; Odd1^tm1Jian; Odd1^tm1RJ
Gene Symbol and Name	Osr1, odd-skipped related transcription factor 1
Gene Synonym(s)
Expressed Gene	lacZ, beta-galactosidase, E. coli
Site of Expression	LacZ expression mimics that of the wild-type targeted gene. During embryogenesis is detected at E7.5 in the intermediate mesoderm, is expanded to the gut endoderm, lung bud mesenchyme and myocardial cells by E9.5, and is activated in developing branchial arches and limb buds by E10.5.
Strain of Origin	129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Chromosome	12
Molecular Note	A targeting construct was designed to insert a lacZ-loxP-neo-loxP cassette into exon 2. The cassette replaces 335 bp of the coding region. The expected protein would contain a functional beta-gal fused to the N-terminal 16 amino acids. X-gal staining detected lacZ activity corresponding to expected activity of the endogenous protein.
Mutations Made By	Rulang Jiang, University of Rochester

Disease/Phenotype

Disease Terms

Research Areas By Phenotype

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

Developmental Biology Research
- Internal/Organ Defects
  - kidney
  - gonads
  - urogenital
  - heart
  - kidneys, gonads, heart
  - adrenal cortex
  - vasculature
  - multiple
  - heart: vasculature
- Mesodermal Defects
- Embryonic Lethality (Homozygous)
Internal/Organ Research
- Kidney Defects
- Heart Abnormalities
- Adrenal Cortex Defects
- Adrenal Medulla Defects
Research Tools
- Genetics Research
  - Tissue/Cell Markers
  - Tissue/Cell Markers: transplantation marker for embryonic and adult tissue
  - Tissue/Cell Markers: multiple
- lacZ Expression
- Developmental Biology Research
  - transplantation marker for embryonic and adult tissue
- Cardiovascular Research
- Internal/Organ Research
Cardiovascular 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: Osr1^tm1Jian/Osr1^tm1Jian
either: (involves: 129S1/Sv * C57BL/6J) or (involves: 129S1/Sv * ICR)

cardiovascular system phenotype

abnormal blood circulation
- at E11.5, blood backflow from the heart into the inflow tract is observed
- at E12, embryos have pooled blood in the liver and major veins

abnormal fetal atrioventricular canal morphology
- at E15.5, atrioventricular junction is malformed

abnormal interatrial septum morphology
- septum primum does not form

abnormal interventricular septum morphology
- at E15.5, ventricular septum is malformed

abnormal pericardium morphology
- at E15.5, mesothelium fails to form complete parietal pericardium

abnormal vein morphology
- at E11.5, embryos have hypoplastic venous valves

absent vitelline blood vessels
- at E12, yolk sac lacks blood circulation

common atrium
- at E15.5, embryos lack a primary atrial septum

dilated heart atrium
- at E11.5, the atria were severely dilated
- later embryos have dilated atria

cellular phenotype

increased kidney apoptosis
- at E10.5, massive cell death is noted in the nephrogenic mesenchyme

embryo phenotype

abnormal mesonephros morphology
- at E11.5, fewer mesonephric tubules are observed and the gonadal ridge is retarded

abnormal Wolffian duct morphology
- at E11.5, the Wolffian duct is often malformed or absent in the posterior trunk region
- significantly fewer mesonephric vesicles are noted at E10.5
- Wolffian duct development is already disrupted at E9.5

absent vitelline blood vessels
- at E12, yolk sac lacks blood circulation

gonadal ridge hypoplasia
- a hypoplastic gonadal ridge is noted at E11.5

rudimentary Wolffian ducts
- at E10.5, disrupted or posteriorly truncated Wolffian ducts are observed
- the Wolffian duct defect is always more severe on the left side than on the right side such that the left duct is often truncated posteriorly

endocrine/exocrine gland phenotype

absent adrenal gland

absent ovary

absent testes

agonadal
- at E15.5-E17.5, all surviving mutants lack gonads

homeostasis/metabolism phenotype

hydrops fetalis
- embryos at late gestation show generalized edema

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance
- most mutants embryos die between 11.5 and 12.5

lethality throughout fetal growth and development, complete penetrance
- approximately 5% survive to E15.5-17.5

renal/urinary system phenotype

abnormal kidney development
- at E10.5 to E11.5, mutant embryos fail to initiate metanephric kidney formation

abnormal metanephric mesenchyme morphology
- at E10.5 to E11.5, no signs of metanephric mesenchyme condensation is observed

abnormal nephrogenic mesenchyme morphogenesis
- at E10.5, massive cell death is noted in the nephrogenic mesenchyme

absent metanephros
- as a result, internal organs (e.g. pancreas and spleen) are displaced but remain morphologically normal
- at E15.5, all mutant embryos lack metanephric kidneys

absent ureteric bud
- at E10.5 to E11.5, ureteric bud formation is absent

increased kidney apoptosis
- at E10.5, massive cell death is noted in the nephrogenic mesenchyme

reproductive system phenotype

absent ovary

absent testes

agonadal
- at E15.5-E17.5, all surviving mutants lack gonads

respiratory system phenotype

abnormal lung morphology
- at E15.5, lung tissue is observed as a compressed mass

Genotype: Osr1^tm1Jian/Osr1^tm1Jian
involves: 129S1/Sv

cellular phenotype

increased metanephric mesenchyme apoptosis
- at E10.5, increased levels of apoptosis are detected in the metanephric mesenchyme relative to heterozygous controls
- however, the levels of apoptosis in metanephric mesenchyme precursor cells are similarly low in E9.5 mutant and control embryos, indicating that apoptosis occurs after the initial metanephric mesenchyme gene expression defects

renal/urinary system phenotype

abnormal mesonephric mesenchyme morphology
- at E9.5 (but not at E8.5), significantly increased levels of apoptosis are detected in the mesenchyme surrounding anterior mesonephric tubules relative to control embryos

abnormal metanephric mesenchyme morphology
- no metanephric mesenchyme condensation is observed at E11.5, unlike in wild-type controls

absent metanephric mesenchyme
- at E11.5, the metanephric mesenchyme fails to form

absent metanephros
- at E10.5, several gene products required for metanephric kidney formation are not expressed in the metanephric mesenchyme region

absent ureteric bud
- at E11.5, ureteric bud formation is completely absent

increased metanephric mesenchyme apoptosis
- at E10.5, increased levels of apoptosis are detected in the metanephric mesenchyme relative to heterozygous controls
- however, the levels of apoptosis in metanephric mesenchyme precursor cells are similarly low in E9.5 mutant and control embryos, indicating that apoptosis occurs after the initial metanephric mesenchyme gene expression defects

embryo phenotype

abnormal mesonephros morphology
- at E10.5, the number and size of mesonephric tubules is significantly smaller than in control embryos
- only anterior mesonephric tubules form

abnormal Wolffian duct morphology
- a decreased diameter of the nephric duct is already seen at E8.5
- at E10.5, the nephric duct fails to migrate toward the cloaca and metanephric mesenchyme, unlike in wild-type embryos
- at E9.5, the nephric duct is thinner and often interrupted

increased metanephric mesenchyme apoptosis
- at E10.5, increased levels of apoptosis are detected in the metanephric mesenchyme relative to heterozygous controls
- however, the levels of apoptosis in metanephric mesenchyme precursor cells are similarly low in E9.5 mutant and control embryos, indicating that apoptosis occurs after the initial metanephric mesenchyme gene expression defects

rudimentary Wolffian ducts
- at E11.5, a nephric duct is often present (on right side but not left), but smaller than normal
- the region between the aorta and nephric duct is significantly reduced

References

Wang Q; Lan Y; Cho ES; Maltby KM; Jiang R. 2005. Odd-skipped related 1 (Odd 1) is an essential regulator of heart and urogenital development. Dev Biol 288(2):582-94PubMed: 16223478 MGI: J:104942

Additional - Osr1^tm1Jian related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated PCR:Osr1 SEP PCR
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred to wildtype siblings or to C57BL/6J inbred mice (Stock No. 000664). Homozygotes die in utero.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129S1-Osr1^tm1Jian/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #009387 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 or Wild-Type for Osr1<tm1Jian>

Related Products and Services

Frozen Mouse Embryo	B6.129S1-Osr1<tm1Jian>/J	$2595.00
Frozen Mouse Embryo	B6.129S1-Osr1<tm1Jian>/J	$2595.00
Frozen Mouse Embryo	B6.129S1-Osr1<tm1Jian>/J	$3373.50
Frozen Mouse Embryo	B6.129S1-Osr1<tm1Jian>/J	$3373.50

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Osr1tm1Jian

Allele Symbol: Osr1tm1Jian

Disease Terms

Research Areas By Phenotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Osr1tm1Jian/Osr1tm1Jianeither: (involves: 129S1/Sv * C57BL/6J) or (involves: 129S1/Sv * ICR)

cardiovascular system phenotype

cellular phenotype

embryo phenotype

endocrine/exocrine gland phenotype

homeostasis/metabolism phenotype

mortality/aging

renal/urinary system phenotype

reproductive system phenotype

respiratory system phenotype

Genotype: Osr1tm1Jian/Osr1tm1Jianinvolves: 129S1/Sv

cellular phenotype

renal/urinary system phenotype

embryo phenotype

References

Additional - Osr1tm1Jian 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

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Osr1^tm1Jian

Allele Symbol: Osr1^tm1Jian

Genotype: Osr1^tm1Jian/Osr1^tm1Jian
either: (involves: 129S1/Sv * C57BL/6J) or (involves: 129S1/Sv * ICR)

Genotype: Osr1^tm1Jian/Osr1^tm1Jian
involves: 129S1/Sv

Additional - Osr1^tm1Jian related