Gene trap capture of a novel mouse gene, jumonji, required for neural tube formation.

Abstract

A mouse mutation, termed jumonji ~mj), was generated by a gene trap strategy. Expression of the trapped gene (jmj gene), as monitored by X-gal staining, was detected predominantly at the midbrain-hindbrain boundary and in the cerebellum, depending on the stage of development. All embryos homozygous for the jmj mutation died before embryonic day 15.5. Some, but not all, of the homozygotes developed an abnormal groove in a region just anterior to the midbrain-hindbrain boundary on the neural plate at embryonic day 8-8.5 and showed a defect in neural tube closure in the midbrain region. Analyses of jmj cDNA revealed that the jmj gene is novel, conserved among vertebrates, and disrupted by vector insertion in the jmj homozygotes.The amino acid sequence deduced from the cDNA shared a portion of significant homology with human retinoblastoma-binding protein RBP-2 and with a putative protein encoded by human gene XE169 that escapes X-chromosome inactivation. These results suggest that jmj gene is essential for normal morphogenesis of the neural tube.

Roles of jumonji and jumonji family genes in chromatin regulation and development

“…During development, very weak expression is observed in the whole embryonic body at embryonic day 8 (E8), after which, a band-like expression pattern is detected at the future midbrain-hindbrain boundary at E8.5. The expression becomes stronger and shows a ring-like pattern after neural tube closure at E9 (Takeuchi et al, 1995). In addition, weak expression is seen in the forebrain and stronger expression is also detected in the bulbous cordis (future outflow tract and right ventricle) of the heart, the primitive pharynx, and around the posterior neuropore in the tail.…”

“…Arrowheads and LE show the equatorial region of the lens vesicle and the lens epithelial cells, respectively. Scale bar ϭ 50 m. trap strategy (Takeuchi et al, 1995).The roles during development have been investigated most intensively among jumonji family genes.…”

“…In the past, we have attempted to identify novel genes that have important roles in development using a mouse gene trap method and have successfully identified jumonji (jmj; Takeuchi et al, 1995;Takeuchi, 1997). The gene was named for the morphology produced by the normal neural groove and abnormal grooves on the neural plates of jmj mutant mice.…”

“…The gene was named for the morphology produced by the normal neural groove and abnormal grooves on the neural plates of jmj mutant mice. The morphology resembles a cross, and "jumonji" means cruciform in Japanese (Takeuchi et al, 1995).…”

“…We first reported that Jmj protein has two conserved domains (Takeuchi et al, 1995). Later, one was further divided into two domains, a jmjN domain and an AT-rich interaction domain (ARID), because there are many proteins that have only one of these two domains (Balciunas and Ronne, 2000;Kortschak et al, 2000).…”