HGM2002 Poster Abstracts: 8. Disease Mechanisms
POSTER NO: 417
Studies on the molecular mechanism of morphogenetic defects in brachydactyly type A-1
1Bo Gao, 1Shengzhen Guo, 1Junwei Meng, 1Anli Shu, 1Chaowen She, 1Jingzhi Guo, 1Guoying Feng, 2Danny Chan, 2Kathryn S.E. Cheah, 1Lin He
Brachydactyly type A-1 (BDA-1), which is characterized by shortening or missing of the middle phalanges, was first identified by Farabee in 1903 as the first recorded example of a human anomaly with Mendelian autosomal-dominant inheritance. In our previous work, we identified three heterozygous missense mutations in IHH, which encodes Indian hedgehog, in three large and unrelated families. In this work, we propose to create a BDA-1 mouse model to study the pathological changes focusing on the development of digits. We constructed the gene targeting vector with the IHH mutation appeared in the third BDA-1 family characterized with short stature. For selecting homologous recombination events flanking exon 1, where the point mutation is located, a selectable marker cassette consisting of a neomycin (neo) gene linked to the pgk promoter flanked by LoxP sites was inserted in intron 1. We are currently underway to make a mouse model. Meanwhile, we constructed the pGEX-2T vector carrying the WT/Mutated N-ihh gene for doing in vitro expression analysis in order to understand the molecular mechanism in the formation of BDA-1.
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