Ptchd3, or Patched domain containing 3, is a gene that contains a conserved patched domain, potentially functioning as a membrane receptor for the hedgehog ligand [1,2]. It was initially identified as a male germ-cell specific gene, and its protein product is present on the surface of mouse, rat, and human sperm [1,2]. The Hedgehog (Hh) signaling pathway, in which Ptchd3 may be involved, is crucial for various biological processes like pattern formation, cell fate determination, proliferation, and differentiation [4]. Mouse models are valuable for studying Ptchd3's function.

Using a Ptchd3 knockout mouse model, researchers found that Ptchd3 is non-essential in mouse development and spermatogenesis. Ptchd3 knockout mice were born and lived normally, with no change in the fertility and sperm production of knockout males. Also, the expression levels of several hedgehog signaling genes were unaffected in mutant testis [1,2]. In human studies, homozygous deletions of PTCHD3 were found in some individuals without ASD or other overt abnormal phenotypes, suggesting it may be non-essential in some humans [3]. Additionally, rare copy number and sequence variants of PTCHD3 were detected, and a novel shorter isoform was characterized [3].

In conclusion, studies using Ptchd3 knockout mouse models and human genetic analyses suggest that Ptchd3 may be a non-essential gene in both mouse and some human biological contexts. These findings contribute to understanding the role of Ptchd3 in normal development and potentially in diseases like autism spectrum disorders, where its deletion did not show a significant association [1,2,3].

References:

1. González Morales, Shaimar R, Liu, Chengjing, Blankenship, Heath, Zhu, Guo-Zhang. 2020. Mouse Ptchd3 is a non-essential gene. In Gene, 763S, 100032. doi:10.1016/j.gene.2020.100032. https://pubmed.ncbi.nlm.nih.gov/34493359/

2. González Morales, Shaimar R, Liu, Chengjing, Blankenship, Heath, Zhu, Guo-Zhang. 2020. Mouse Ptchd3 is a non-essential gene. In Gene: X, 5, 100032. doi:10.1016/j.gene.2020.100032. https://pubmed.ncbi.nlm.nih.gov/32550558/

3. Ghahramani Seno, Mohammad M, Kwan, Benjamin Y M, Lee-Ng, Ka Ki M, Marshall, Christian R, Scherer, Stephen W. 2011. Human PTCHD3 nulls: rare copy number and sequence variants suggest a non-essential gene. In BMC medical genetics, 12, 45. doi:10.1186/1471-2350-12-45. https://pubmed.ncbi.nlm.nih.gov/21439084/

4. Fan, Jun, Akabane, Hiroto, Zheng, Xuehai, Yang, Jing, Zhu, Guo-Zhang. 2007. Male germ cell-specific expression of a novel Patched-domain containing gene Ptchd3. In Biochemical and biophysical research communications, 363, 757-61. doi:. https://pubmed.ncbi.nlm.nih.gov/17904097/