{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T05:43:01Z","timestamp":1792734181707,"version":"4.5.0"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,12,21]]},"abstract":"<jats:p>\n                    Formation of the mammalian secondary palate is a highly regulated and complex process whose impairment often results in cleft palate, a common birth defect in both humans and animals. Loss-of-function analysis has linked a growing number of genes to this process. Here we report that\n                    <jats:italic>Lhx8<\/jats:italic>\n                    , a recently identified LIM homeobox gene, is expressed in the mesenchyme of the mouse palatal structures throughout their development. To test the function of\n                    <jats:italic>Lhx8 in vivo<\/jats:italic>\n                    , we generated a mutant mouse with a targeted deletion of the\n                    <jats:italic>Lhx8<\/jats:italic>\n                    gene. Our analysis of the mutant animals revealed a crucial role for\n                    <jats:italic>Lhx8<\/jats:italic>\n                    in palatogenesis. In\n                    <jats:italic>Lhx8<\/jats:italic>\n                    homozygous mutant embryos, the bilateral primordial palatal shelves formed and elevated normally, but they often failed to make contact and to fuse properly, resulting in a cleft secondary palate. Because development of other craniofacial structures appeared normal, the impaired palatal formation in\n                    <jats:italic>Lhx8<\/jats:italic>\n                    -mutant mice was most likely caused by an intrinsic primary defect in the mesenchyme of the palatal shelves. The cleft palate phenotype observed in\n                    <jats:italic>Lhx8<\/jats:italic>\n                    -mutant mice suggests that\n                    <jats:italic>Lhx8<\/jats:italic>\n                    is a candidate gene for the isolated nonsyndromic form of cleft palate in humans.\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.26.15002","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"15002-15006","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":142,"title":["Isolated cleft palate in mice with a targeted mutation of the LIM homeobox gene\n                    <i>Lhx8<\/i>"],"prefix":"10.1073","volume":"96","author":[{"given":"Yangu","family":"Zhao","sequence":"first","affiliation":[{"name":"Laboratory of Mammalian Genes and Development, National Institute of Child Health and Human Development, Bethesda, MD 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