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
¹Bio-X Life Science Research Center, Shanghai Jiao Tong University, Hao Ran Building 501, No 1954, HuaShan Road, Shanghai, P.R.China, ²Department of Biochemistry, Hong Kong University, 3/F, Li Shu Fan Building,5 Sassoon Road, Hong Kong

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.