Proviral inactivation of the Npat gene of Mpv 20 mice results in early embryonic arrest.
The Mpv 20 transgenic mouse strain was created by infection of embryos with a defective retrovirus. When Mpv 20 heterozygous animals were crossed, no homozygous neonatal mice or midgestation embryos were identified. When embryos from heterozygous crosses were cultured in vitro, approximately one quarter arrested as uncompacted eight-cell embryos, indicating that proviral insertion resulted in a recessive lethal defect whose phenotype was manifest very early in development. Molecular cloning of the Mpv 20 insertion site revealed that the provirus had disrupted the Npat gene, a gene of unknown function, resulting in the production of a truncated Npat mRNA. Expression of the closely linked Atm gene was found to be unaffected by the provirus.
Di Fruscio
M
M
Ottawa Regional Cancer Centre, Ontario, Canada.
Weiher
H
H
Vanderhyden
B C
BC
Imai
T
T
Shiomi
T
T
Hori
T A
TA
Jaenisch
R
R
Gray
D A
DA
D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D018797:Cell Cycle Proteins; D002970:Cleavage Stage, Ovum; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins; D003673:Defective Viruses; D018507:Gene Expression Regulation, Developmental; D051379:Mice; D008822:Mice, Transgenic / Q000196:embryology*; D008969:Molecular Sequence Data; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics*; D011533:Proviruses; D012190:Retroviridae / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D016662:Virus Integration
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C101693:NPAT protein, human; D009687:Nuclear Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases