Pathways involved in pony body size development

Abstract

Background: The mechanism of body growth in mammal s is poorly understood. Here, we report the regulat ory networks involv ed in body growth through analyzing transcriptomes of pituitary and epiphyseal tissues of Debao pon ies and Mongolian horse s at juvenile and adult stages .

Results: We found that Growth hornome receptor ( GHR ) was expressed little in long bones though Growth hornome ( GH ) w as highly expressed in Debao pon ies compared with Mongolian horses. Moreover, m -RAS and ATF3 , involved in the GHR pathway , were found to be significant ly downreg ulated in juvenile pon ies , which slowed the proliferation of bone osteocytes. However, WNT2 and PLCβ2 were obviously upregulated in juvenile Debao ponies, which led to premature mineralization of bone extracellular matrix. Furthermore, we found that the WNT/Ca 2+ pathway may be responsible for the regulation of body growth . W e then demonstrated that GHR was lack ing in long bone s of Debao ponies using RT-qPCR and Western blot. Treatment with WNT antagonist 1 decrease d expression of the WNT pathway (P ≤ 0.05) in vitro. The transduction of ATDC5 cells with GHR-RNAi lentivirus decrease d expression of the GHR pathway (P ≤ 0.05). Additionally, detection of plasma hormone concentration s showed that the pon ies had higher levels of IGF-1 as juvenile s and GH in adulthood than Mongolian horse s , indicating that the hormone regulation in Debao pon ies differ s from that in Mongolian horse s .

Conclusion: Our work provides an insight into the genetic regulation for dwarf growth in mammals and a reference for therapeutic strategy for dwarfism.