Morphological features of mutant rat, IS-Tlk/Kyo, fetuses with caudal vertebral anomalies.

IS-Tlk/Kyo, a rat mutant strain derived from IS/Kyo strain, exhibits a kinked and/or short tail, in addition to a congenital anomaly of the lumbar vertebrae that is a hallmark of IS/Kyo rats. Homozygotes (Tlk/Tlk) of Tlk dominant gene are known to die during embryonic development. The present report deals with the morphological features of heterozygous IS-Tlk/Kyo rat fetuses in comparison with those of IS/Kyo rat fetuses. One of the morphological features was a high incidence of tail vertebral anomalies in IS-Tlk rats (81.6% versus 0% in IS/Kyo rats). Significantly low values in number of live fetuses and ossified 5th sternebra and sacral and caudal vertebrae were observed in IS-Tlk/Kyo rats compared with those in IS/Kyo rats as well as a low incidence of fetuses with ventral septal defects in IS-Tlk/Kyo (0% versus 54.4% in IS rats). These results suggest that the Tlk gene may be involved in the formation of the vertebral centra and the ventral septum when it expresses on the genetic background of the IS rat.

Changes in blood parameters and coagulation-related gene expression in pregnant rats.

The present study examined changes in maternal blood parameters, particularly those related to blood coagulation, as well as alterations in blood coagulation-related gene expression in the liver during gestation in rats. Fibrinogen concentration and platelet count increased as pregnancy progressed whereas prothrombin time and overall activity of vitamin-K-dependent coagulation factors decreased before delivery, suggesting a physiologic response to prevent prolonged bleeding at parturition. Conversely, compared with values for nonpregnant rats, activated partial thromboplastin time was prolonged before delivery and antithrombin time was significantly higher during fetal organogenesis and thereafter, indicating a mechanism to prevent the development of deep tissue thrombosis in dams. DNA microarray analysis revealed no differences in coagulation-related gene expression in the liver on gestation day 13 between pregnant and nonpregnant rats, whereas the gene expression of various fibrinogen-related factors, coagulation factors II and X, and the anticoagulation factor-related factor leuserpin 2 were increased on gestational day 19. In addition, changes similar to those reported previously in pregnant rats were confirmed. The data obtained from the present study can be used as background data for effective evaluation of reproductive toxicology in rats, and they suggest that the rat is a useful animal model for investigating the mechanisms of disorders in the blood coagulation system that can occur during late pregnancy in women.