ABSTRACT The present study aimed at elucidating the cause of pre-weaning mortality of fpl/fpl rats having fusion of the right lung lobes with hypoplasia of the intermediate lobe and many other associated malformations. In the first experiment, fpl/fpl pups were examined for postnatal viability and growth. Cumulative mortality of fpl/fpl pups obtained from three types of mating pairs was 13.8-30.8% on day 0 of lactation and was raised to 41.9-76.7% on day 4. However, only few deaths were noted thereafter. Body weights of surviving fpl/fpl pups were significantly lower than those of + / - littermates through the lactation period. In the second experiment, moribund or dead fpl/fpl newborns at birth were closely examined for abnormalities in general condition and necropsied. Their lungs were weighed and examined for histological abnormalities. Several findings obtained from the fpl/fpl newborns demonstrated the occurrence of respiratory failure. They were decreased frequency of respiration, cyanosis, hepatization of the lung and inflation of the stomach by air. Lung weights of these newborns were significantly lower than those of + / - littermates. Histological examination of the lungs of dying fpl/fpl newborns revealed partial atelectasis occurred in the regions where fusion of lobes as well as hypoplasia of the lobe was grossly observed. In these lungs, however, epithelial maturation was apparently normal and hyaline membrane was not formed. These observations suggest that reduced gas-exchanging capacity related to lung mal- formations leads fpl/fpl newborns to die of respiratory insufficiency in their early post- natal age.
ABSTRACT The effect of phenytoin on morphology of otoliths was investigated in rat fetuses. Pregnant rats were administered with phenytoin (PHT) SO, 100 and 200 mg/kg/day on days 11-14 of pregnancy and the fetuses were removed on day 20 of pregnancy. Methyl salicylate cleared specimens were prepared and the otoliths were scored for morphological completeness. Otolith score decrease was observed only in utricles of the fetuses treated with PHT 200 mg/kg/day with a statistical difference. The most remarkable morphological change in otoliths was that the utricular otolith and the saccular otolith were connected and the otoconial crystals were visible between utricular and saccular otoliths. The frequency of this conjoined utricule and saccule was about 30% of the fetuses treated with PHT 200 mg/kg/day. From these results, the threshold level of PHT for induction of otolith abnormalities was estimated to be between 100 and 200 mg/kg/day.
ABSTRACT Recent knowledge on molecular basis of several contiguous gene syndromes as multiple anomalies syndromes, such as Prader-Willi syndrome (PWS), Angelman syn- drome (AS), Beckwith-Wiedemann syndrome (BWS), tricho-rhino-phalageal syndrome types I (TRPS I) and I1 (TRPS I1 or LGS), and complex glycerol kinase deficiency (CGKD), are reviewed. Based on the results of DNA deletion studies and on the evidence for the genomic imprinting mechanism of both PWS and AS, a model for the occurrence of the two syndromes is proposed. Also, a strategy of the microdissection/microcloning technique as a reverse genetics technique, i.e., direct cloning of chromosomal DNAs from a defined region of human chromosome, particularly for the cloning of the exostosis gene in TRPS, is presented.