Apoptotic degeneration in the arhinencephalic brain of the mouse mutant Pdn/Pdn.

ABSTRACT

The homozygotes of a mouse strain with genetic polydactyly (Polydactyly Nagoya, Pdn) exhibit arhinencephaly and various brain malformations. In the present experiment, abnormal apoptotic degeneration in the arhinencephalic brain of Pdn/Pdn embryos and newborns was investigated immunohistochemically and by molecular genetic techniques. Polyclonal antibody against single-stranded DNA detected the nuclei of programmed dying cells (apoptotic cells) specifically in the interdigital necrotic zone of the normal mouse limb plate on day 14 of gestation. We used this antibody against single-stranded DNA to investigate the apoptotic degeneration in Pdn/Pdn brain. Abnormal apoptosis was observed in the infralimbic cortical plate, hypothalamus and periventricular thalamus on day 0 after birth in Pdn/Pdn brains. The TRPM-2 gene, which has been considered to mediate apoptosis, was expressed in the developing normal and Pdn/Pdn brains. TRPM-2 gene expressions in the brain stem and cerebellum of arhinencephalic Pdn/Pdn fetuses and newborns were higher than those of +/+ littermates. From these facts, it was suggested that the abnormal apoptosis caused a large amount of cell loss in the arhinencephalic mouse brain, and this cell loss induced the expansion of the ventricle, followed by the hydrocephaly.