Species Differences in BMP Signaling

There are both similarities and important differences between species in regulation in BMP signaling and consequences of gene knockouts in this pathway. Both mice and sheep with knockout mutations in GDF9 are infertile. In contrast to the dramatic consequences of homozygous mutations of BMP15 in sheep, targeted deletion of the second exon of Bmp15 in the mouse has little effect on folliculogenesis (30). However, the knockout mice are sub-fertile due to defects in the ovulation process and early embryo development. Reasons for the difference are not clear, but may relate to the relative importance of BMP15 and GDF9 in regulating follicle development in the different species. Another possibility is differential effects of the gene disruptions on processing and formation of GDF9/BMP15 homo- and heterodimers (22). BMP15 seems essential for human fertility (31). Two sisters with hypergonadotropic ovarian failure due to ovarian dysgenesis carry a non-conservative amino acid substitution in the promoter region of BMP15 (tyr235Cys) which acts in a dominant negative fashion by altering processing of BMP15.

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