Homez, a homeobox leucine zipper gene, encodes a protein with an unusual structure featuring three atypical homeodomains, two leucine zipper-like motifs, and an acidic domain [2]. It is ubiquitously expressed in human and murine tissues, and phylogenetically conserved among mammalian species [1,2]. The gene belongs to a subset within the superfamily of homeobox-containing proteins along with ZHX family members [2]. It may be involved in multiple biological processes, and its study via genetic models can provide insights into its functions.

Using Nuclease technology technology to generate Homez mutant mice, it was found that Homez knockout males were viable, with no differences in body and testis weight compared to wild-type. Mating between mutant males and wild-type females produced normal litter sizes, and complete spermatogenesis and mature spermatozoa were observed in knockout males, indicating that Homez is dispensable for male fertility and germ cell development [1]. In Xenopus laevis, interference with Homez function by injecting an antisense morpholino oligonucleotide disrupted the expression of late neuronal markers, suggesting a role in neuronal development downstream of proneural/neurogenic genes [3]. In Chinese patients with isolated ventricular septal defect, two novel heterozygous missense mutations in Homez gene exon-2 were identified, which may be directly linked to the disease etiology [4].

In conclusion, Homez has diverse functions as revealed through model-based research. In mouse models, it is not essential for male fertility. In Xenopus, it plays a role in neurogenesis, and in humans, its mutations are associated with isolated ventricular septal defect. These findings contribute to understanding biological processes and disease mechanisms related to Homez.

References:

1. Yue, Qiuling, Yu, Lina, Liu, Wenwen, Yan, Guijun, Bai, Shun. . Homeodomain protein HOMEZ is dispensable for male fertility in mice. In Translational andrology and urology, 11, 750-760. doi:10.21037/tau-21-1169. https://pubmed.ncbi.nlm.nih.gov/35812194/

2. Bayarsaihan, Dashzeveg, Enkhmandakh, Badam, Makeyev, Aleksandr, Leckman, James F, Ruddle, Frank H. 2003. Homez, a homeobox leucine zipper gene specific to the vertebrate lineage. In Proceedings of the National Academy of Sciences of the United States of America, 100, 10358-63. doi:. https://pubmed.ncbi.nlm.nih.gov/12925734/

3. Ghimouz, Rym, Bar, Isabelle, Hanotel, Julie, Thelie, Aurore, Bellefroid, Eric J. 2011. The homeobox leucine zipper gene Homez plays a role in Xenopus laevis neurogenesis. In Biochemical and biophysical research communications, 415, 11-6. doi:10.1016/j.bbrc.2011.09.138. https://pubmed.ncbi.nlm.nih.gov/22001922/

4. Xuan, Chao, Jia, Ke-Gang, Wang, Bin-Bin, Ma, Xu, He, Guo-Wei. 2013. Identification of two novel mutations of the HOMEZ gene in Chinese patients with isolated ventricular septal defect. In Genetic testing and molecular biomarkers, 17, 390-4. doi:10.1089/gtmb.2012.0435. https://pubmed.ncbi.nlm.nih.gov/23574532/