HOXB-8 GAIN-OF-FUNCTION TRANSGENIC MICE EXHIBIT ALTERATIONS IN THE PERIPHERAL NERVOUS-SYSTEM

To understand the developmental role of Hoxb-8, this relatively 5' Her b gene was ectopically expressed in embryonic regions where only more 3' Hox genes are normally expressed. Hoxb-8 coding sequences driven by a retinoic acid receptor beta 2 promoter fragment were introduced in the mouse germ line by pronuclear injection. The promoter was chosen w ith the aim to extend rostrally the expression domain of the gene in n eurectoderm and mesoderm at the time of development when Hox gene expr ession domains are being established. Embryos developing from DNA-inje cted zygotes, and from transgenic mouse lines were analyzed. Pattern a lterations were observed in transgenic embryos, some of which involved the peripheral nervous system. Spinal ganglia in the mouse are first detectable around embryonic day 9.5, By day 11.5, the first of these g anglia (C1, Froriep's ganglion) has degenerated in the mouse and other amniotes. In contrast, this first ganglion did persist in the Hoxb-8 gain-of-function transgenic mice. We have started to take advantage of the phenotype of transgenic versus wild-type embryos to understand th e mechanisms underlying the ontogeny and degeneration of Froriep's gan glion in wild-type mice, and the role of Hoxb-8 in C1 maintenance in t ransgenic embryos. The present work describes a morphological, histolo gical and immunocytological analysis of both the degenerating and the permanent C1, and a preliminary characterization of the axonal extensi ons from the transgenic C1. We discuss the methodology of generating g ain-of-function transgenic mice to study the genetics of pattern forma tion along the antero-posterior axis, and the usefulness of analyzing these particular Hoxb-8 transgenic embryos to understand some aspects of the ontogenesis and development of the upper cervical dorsal root g anglia.