Transient absence of CD44 expression and delay in development by anti-CD44 treatment during ontogeny: a surrogate of an inducible knockout?
Because the lack of some adhesion molecules induced by site-directed mutagenesis has been described to be lethal, whereas the lack of others apparently has no effect, we were interested in seeing whether the developing organism might gradually adapt to the absence of adhesion molecules. Therefore, we chose a form of transient interference by i.v. injection of antibody into pregnant rats. As a model, we selected CD44, which has been reported to play a key role during embryogenesis. Rats received either an antibody recognizing an epitope on the CD44 standard isoform (CD44s) or on exon v6 (CD44v6). In the presence of anti-CD44s, delivery was frequently delayed, and intrauterine abortions were often observed. The fetuses were smaller, particularly the anlage of the hair follicle of the whisker, and the formation of alveoli in the lung, of the tubular system of the kidney, and of villi in the gut was delayed. The development of fetuses receiving anti-CD44v6 was hampered until days 16-18 of gestation. Immunodetection revealed a weaker expression of the target molecules at the implantation site and the complete absence of CD44s and CD44v6 expression in fetal tissue until day 12. During the late stages of gestation, the expression pattern of CD44 resembled that of 2-3-day-younger fetuses of untreated rats. Interestingly, degradation of hyaluronate was also delayed, particularly in the kidney. Thus, the diaplacental antibody passage was very efficient and should make it possible to obtain a clearly defined and differentiated concept of the requirements for the CD44 molecule during ontogeny and also for fail-safe mechanisms. Both experiences may be missed in the knockout proper.
Zöller
M
M
Department of Tumor Progression and Immune Defense, German Cancer Research Center, Heidelberg, Germany. M.Zoeller@DKFZ-Heidelberg.DE
Herrmann
K
K
Büchner
S
S
Seiter
S
S
Claas
C
C
Underhill
C B
CB
Möller
P
P
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D010064:Embryo Implantation / Q000187:drug effects; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D018960:Hyaluronan Receptors / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*; D010920:Placenta / Q000187:drug effects; D010929:Placentation; D011247:Pregnancy; D051381:Rats
D000906:Antibodies; D018960:Hyaluronan Receptors