The rat small eye strain (rSey) lacks eyes and nose in the homozygote, and is similar to the mouse Sey strain with mutations in the Pax-6 gene. We isolated Pax-6 cDNA clones from an rSey homozygote library, and found an internal deletion of about 600 basepairs in the serine/threonine-rich domain. At the genomic level, a single base (G) insertion in an exon generates an abnormal 5' donor splice site, thereby producing the truncated mRNA. Anterior midbrain crest cells in the homozygous rSey embryos reached the eye rudiments but did not migrate any further to the nasal rudiments, suggesting that the Pax-6 gene is involved in conducting migration of neural crest cells from the anterior midbrain.

Lipopolysaccharide (LPS) is a potent stimulator of monocytes and macrophages, causing secretion of tumor necrosis factor ␣ (TNF-␣) and other inflammatory mediators. Given the deleterious effects to the host of TNF-␣, it has been postulated that TNF-␣ gene expression must be tightly regulated. The nature of the nuclear factor(s) that control TNF-␣ gene transcription in humans remains obscure, although NF-B has been suggested. Our previous studies pertaining to macrophage response to LPS identified a novel DNA-binding domain located from ؊550 to ؊487 in the human TNF-␣ promoter that contains transcriptional activity, but lacks any known NF-B-binding sites. We have used this DNA fragment to isolate and purify a 60-kDa protein binding to this fragment and obtained its aminoterminal sequence, which was used to design degenerate probes to screen a cDNA library from THP-1 cells. A novel cDNA clone (1.8 kb) was isolated and fully sequenced. Characterization of this cDNA clone revealed that its induction was dependent on LPS activation of THP-1 cells; hence, the name LPS-induced TNF-alpha factor (LITAF). Inhibition of LITAF mRNA expression in THP-1 cells resulted in a reduction of TNF-␣ transcripts. In addition, high level of expression of LITAF mRNA was observed predominantly in the placenta, peripheral blood leukocytes, lymph nodes, and the spleen. Finally, chromosomal localization using fluorescence in situ hybridization revealed that LITAF mapped to chromosome 16p12-16p13.3. Together, these findings suggest that LITAF plays an important role in the activation of the human TNF-␣ gene and proposes a new mechanism to control TNF-␣ gene expression.

A new gene, nel, was isolated from a 9-day-old chick embryonic cDNA library. The gene encodes a protein of 835 amino acids (93,407 M,

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