Molecular Analysis of the Sex Hormone-Binding Globulin Gene in the Rat Hypodactylous Mutation (<i>Hd</i>)

Liška, František; Gösele, C.; Křen, V.; Hübner, N.; Křenová, D.

doi:10.14712/fb2004050020063

Fol. Biol. 2004, 50, 63-68

https://doi.org/10.14712/fb2004050020063

Molecular Analysis of the Sex Hormone-Binding Globulin Gene in the Rat Hypodactylous Mutation (Hd)

František Liška¹, C. Gösele^2,3, V. Křen^1,4, N. Hübner², D. Křenová¹

¹Institute of Biology and Medical Genetics, Charles University, Prague, Czech Republic
²Max Delbrück Centre for Molecular Medicine, Berlin, Germany
³Max Planck Institute for Molecular Genetics, Berlin, Germany
⁴Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic

Received April 2004
Accepted April 2004

Sex hormone-binding globulin or ABP/SHBG is an extracellular androgen and oestrogen carrier. In the rat, ABP/SHBG is secreted by Sertoli cells of the testis and is thought to regulate androgen bioavailability in the male reproductive tract. During ontogenesis, ABP/SHBG is expressed in many mesoderm-derived tissues, including interdigital mesenchyme of the developing autopodium. Shbg is thus a candidate for Hd, comprising autopodium (hand and foot) reduction and male sterility resulting from spermatogenesis impairment. Moreover, linkage mapping of Hd revealed that an intragenic marker for Shbg, D10Wox12, was non-recombinant with Hd. Sequencing of the entire coding sequence of Shbg failed to identify any variation in hypodactylous animals, distinct from two control strains. However, RT-PCR analysis revealed a significantly higher level of the Shbg transcript in hypodactylous rats compared to SHR controls. Whether Shbg expression is upregulated due to a cis-acting mutation in regulatory elements of the Shbg gene or it is a secondary result of spermatogenesis failure remains to be determined.