Pappa2, also known as pregnancy-associated plasma protein-A2, is a protease that specifically cleaves IGF-binding protein (IGFBP)-3 and-5. By doing so, it regulates the bioavailability of insulin-like growth factor-1 (IGF-1), an important mediator in the growth hormone (GH)-IGF axis, which is central to human growth physiology [1].

In mouse models, Pappa2 deletion leads to various effects. At 10 and 19 weeks of age, there are slightly reduced trabecular parameters, but by 19 weeks, female deletion mice show increased cortical tissue mineral density, and at 30 weeks, this trait increases slightly in both sexes. Cortical area fraction is increased at all ages. Deletion also increases circulating IGFBP-5 levels and reduces markers of bone turnover, indicating its role in regulating bone structure and mass [2]. Pappa2 deletion affects male but not female fertility in mice. The interval between the births of the first and second litters is significantly longer in deletion males, though the underlying mechanism is unclear [3].

In conclusion, Pappa2 plays a crucial role in regulating IGF-1 bioavailability, which impacts multiple biological processes. Mouse models with Pappa2 deletion have revealed its significance in bone development and male fertility. These findings contribute to understanding growth-related disorders, bone-related diseases, and reproductive health [1,2,3].

References:

1. Fujimoto, Masanobu, Andrew, Melissa, Dauber, Andrew. 2020. Disorders caused by genetic defects associated with GH-dependent genes: PAPPA2 defects. In Molecular and cellular endocrinology, 518, 110967. doi:10.1016/j.mce.2020.110967. https://pubmed.ncbi.nlm.nih.gov/32739295/

2. Christians, Julian K, Amiri, Neilab, Schipilow, John D, Zhang, Steven W, May-Rashke, Kristyna I. 2018. Pappa2 deletion has sex- and age-specific effects on bone in mice. In Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society, 44, 6-10. doi:10.1016/j.ghir.2018.10.006. https://pubmed.ncbi.nlm.nih.gov/30445407/

3. Christians, Julian K, King, Avery Y, Rogowska, Monika D, Hessels, Sonia M. 2015. Pappa2 deletion in mice affects male but not female fertility. In Reproductive biology and endocrinology : RB&E, 13, 109. doi:10.1186/s12958-015-0108-y. https://pubmed.ncbi.nlm.nih.gov/26416573/