104. LRGUK – A NOVEL GENE INVOLVED IN MALE FERTILITY
K. Deboer A , C. Borg A , D. Jamsai A , R. Prawer A , V. Adams B and M. O’Bryan AA Deptartment of Anatomy and Developmental Biology, Monash University, Melbourne, VIC, Australia.
B The Australia Phenomics Facility, The Australian National University, Canberra, ACT, Australia.
Reproduction, Fertility and Development 22(9) 22-22 https://doi.org/10.1071/SRB10Abs104
Published: 6 September 2010
Abstract
Infertility affects a large number of Australian men. The causative factor in many of these cases is likely to be genetic in origin. As such, the identification and characterisation of novel genes involved in male fertility represents an important area of research. We have undertaken an N-ethyl-nitrosourea (ENU) mutagenesis screen to identify novel genes involved in male fertility. From this screen we have identified a mouse line that we have designated ‘Kaos’. Male mice that are homozygous for the Kaos mutation are infertile as a result of severely disrupted spermatogenesis, with Kaos homozygote males containing only 20% of the normal number of elongated spermatids in their testes, when examined by nuclear resistance to Triton X-100 solubilisation. In contrast, Kaos homozygote females are fertile. To identify the Kaos causal mutation, we used a combination of DNA linkage analysis and candidate gene sequencing. A point mutation was identified in exon 14 of the Leucine-rich Repeats and Guanylate Kinase domain containing (Lrguk) gene, which introduces a pre-mature stop codon into the Lrguk coding sequence. The function of the LRGUK protein is currently unknown. However preliminary expression and phenotype analysis suggests that Lrguk may have a role in spermiogenesis (i.e. haploid germ cell development). The deduced LRGUK protein contains several potentially important domains including a Guanylate Kinase-like (GK) domain and a number of leucine-rich repeats. The GK-like domain has some homology to guanylate kinase, a metabolic enzyme involved in purine nucleotide metabolism. Studies are currently underway to determine whether the LRGUK protein possesses guanylate kinase enzyme activity. In other proteins, the GK-like domain has evolved into mediating protein-protein interactions (1), and current studies are also aimed at examining this possibility. These studies should provide insight into the function of LRGUK and its role in spermatogenesis.
(1) Montgomery J, et al. (2004). MAGUKs in synapse assembly and function: an emerging view. Cell Mol Life Sci. 61(7–8): 911–929.
