B6.129S1-Osr1^tm1Jian/J

Stock number: 009387
Research areas: Cardiovascular Research, Developmental Biology Research, Internal/Organ Research, Research Tools

Description

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).

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.

Allele

Symbol: Osr1^tm1Jian
Name: targeted mutation 1, Rulang Jiang
MGI accession ID: MGI:3613748
Generation method: Targeted
Attributes: Reporter; Null/Knockout
Marker symbol: Osr1
Marker name: odd-skipped related transcription factor 1
Chromosome: 12
Strain of origin: 129S1/Sv-Oca2⁺ Tyr⁺ Kitl⁺
Expressed genes: 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.
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.