Homez-KO Mouse

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 CRISPR/Cas9 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/