The targeted mutation deletes the region of the mouse Hpgd locus corresponding to amino acids 167-266 of the human gene. These mice may be useful in studying the role of Hpgd and prostaglandin E2 (PGE2) in closure of the ductus arteriosus and clinical management of ductus-dependant congenital heart defects.
Beverly H Koller, University of North Carolina at Chapel Hill
The targeted mutation deletes the region of the mouse Hpgd locus corresponding to amino acids 167-266 of the human gene. Heterozygous mice are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. Homozygous (Pgdh-/-) mice exhibit failure of the ductus arteriosus to close; resulting in perinatal lethality within 12-48 hours after birth due to congestive heart failure. Homozygotes are viable only if newborn pups are given indomethacin (6mg/kg) within 12 hours of birth (and these surviving homozygous males are fertile, but surviving homozygous females are infertile). These mice may be useful in studying the role of Hpgd and prostaglandin E2 (PGE2) in closure of the ductus arteriosus and clinical management of ductus-dependant congenital heart defects.
A targeting vector was designed to replace a portion of the mouse Hpgd locus (corresponding to amino acids 167-266 in human 15-hydroxyprostaglandin dehydrogenase (15-PGDH)) with a neomycin-resistance cassette (PGK-Neo). This construct was electroporated into 129P2/OlaHsd-derived E14TG2a embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts and the resulting chimeric mice were bred to C57BL/6J to establish the colony. These mutant mice were backcrossed at least 15 generations to C57BL/6 mice prior to arrival at the MMRRC at The Jackson Laboratory. Upon arrival, mice were bred to C57BL/6J for at least one generation to establish the colony.
|Allele Name||targeted mutation 1, Beverly H Koller|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Hpgd, hydroxyprostaglandin dehydrogenase 15 (NAD)|
|Strain of Origin||129P2/OlaHsd|
|General Note||Phenotypic Similarity to Human Syndrome: Patent Ductus Arteriosus in homozygous mice (J:74466)|
|Molecular Note||The gene was disrupted by replacement of sequences corresponding to amino acids 167-266 of the human protein with a PGK-neo cassette via homologous recombination. Absence of gene expression in homozygous mutant animals was confirmed by Northern blot analysis of lung and liver RNA.|
|Mutations Made By|| |
Michael Backlund, University of North Carolina-Chapel Hill
When maintained as a live colony, heterozygous mice are bred with wildtype siblings or C57BL/6J inbred mice. Homozygous mice exhibit perinatal lethality within 12-48 hours after birth due to congestive heart failure. Homozygotes are viable only if newborn pups are given indomethacin (6mg/kg) within 12 hours of birth (and these surviving homozygous males are fertile, but surviving homozygous females are infertile).
When using the B6.129P2-Hpgdtm1Bhk/Mmjax mouse strain in a publication, please cite the originating article(s) and include MMRRC stock #32028 in your Materials and Methods section.
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