| First Author | Lundberg YW | Year | 2004 |
| Journal | Mamm Genome | Volume | 15 |
| Issue | 5 | Pages | 361-9 |
| PubMed ID | 15170225 | Mgi Jnum | J:90097 |
| Mgi Id | MGI:3042519 | Doi | 10.1007/s00335-004-2345-9 |
| Citation | Lundberg YW, et al. (2004) Mapping a chromosomal locus for valproic acid-induced exencephaly in mice. Mamm Genome 15(5):361-9 |
| abstractText | Human neural tube defects (NTDs) are among the most common congenital defects. They have a highly heterogeneous etiology, and, in addition to those seen in association with genetic syndromes, there are also NTDs induced by pharmaceutical compounds in utero, such as the widely used anti-epileptic drug valproic acid (VPA). Although familial studies have suggested a genetic contribution to VPA-induced NTDs, this trait has not been adequately studied, nor have the responsible genetic factors been identified. We generated a series of mouse crosses and backcrosses using the highly inbred SWV/Fnn and C57BL/6J strains, in order to identify possible chromosomal loci contributing to VPA sensitivity. When exposed to a high dose of sodium VPA (600 mg/kg) via maternal intraperitoneal injection on gestational day E8.5, the fetuses manifested exencephaly in a strain-dependent manner. Our data show an autosomal recessive trait, plus a gender-related effect or an overall X-Chromosome (Chr) effect, as being primarily responsible for determining sensitivity to VPA-induced exencephaly. Genome scanning and further linkage analysis of 131 exencephalic backcross fetuses identified a major locus linked to D7Mit285 (p < 2 x 10(-6)), exceeding the threshold for significant linkage. These results suggest a major chromosomal locus associated with the sensitivity to VPA-induced exencephaly in mice. |
