The high-molecular-mass kininogen deficient rat expresses all kininogen mRNA species, but does not export the high-molecular-mass kininogen synthesized.
The Katholiek substrain of Brown Norway (BN/Kat) rats exhibits a very low level of circulating high-molecular-mass (HMW) kininogen and a partial deficiency in plasma prekallikrein. Northern blot analysis of liver RNA revealed that HMW kininogen and prekallikrein mRNAs are present in these rats with a similar size and abundance compared to control Brown Norway (BN/Orl) rats. The low-molecular-mass kininogen mRNA, encoded by the same kininogen gene as HMW kininogen mRNA by alternative splicing, is detected in both strains by dideoxynucleotide limited primer extension analysis. Measurement of HMW kininogen by radioimmunoassay was performed in liver subcellular fractions. It reveals that, in contrast to its absence in the cytosolic fraction, HMW kininogen in deficients rats is slightly more abundant in the microsomal fraction, than in control rats. These observations exclude both an abnormality at the level of gene transcription and a major structural modification of the transcribed RNA and of the synthesized HMW kininogen. They favour the hypothesis of an abnormal intracellular transport of the HMW kininogen in deficient rats.
Lattion
A L
AL
INSERM U36, Paris, France.
Baussant
T
T
Alhenc-Gelas
F
F
Seidah
N G
NG
Corvol
P
P
Soubrier
F
F
D000818:Animals; D015152:Blotting, Northern; D015153:Blotting, Western; D015342:DNA Probes; D007704:Kininogens / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics*; D008099:Liver / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology; D015345:Oligonucleotide Probes; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics*; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D013045:Species Specificity; D014158:Transcription, Genetic
D015342:DNA Probes; D007704:Kininogens; D015345:Oligonucleotide Probes; D012333:RNA, Messenger