Disruption of the mouse phospholipase C-beta1 gene in a beta-lactoglobulin transgenic line affects viability, growth, and fertility in mice.

A recessive insertional mutation was identified in one line of transgenic mice for the caprine beta-lactoglobulin (betaLG) gene. High mortality after birth, a significant reduction in postnatal growth and adult body size, changes in the morphometric features of the head, and infertility are the most prominent phenotypic traits of the mutant animals. Molecular cloning and sequencing of the transgene insertion site showed that 22 copies of the betaLG transgene are inserted in an intronic region of the phospholipase C-beta1 (PLC-beta1) gene, which plays a pivotal role in modulating different cellular functions. As a result of the insertional mutation (PLC-beta1(betaLG) mutation), a hybrid messenger RNA (mRNA) between the mouse PLC-beta1 and the goat betaLG genes is transcribed. The tissue-specific pattern of expression of this hybrid mRNA in PLC-beta1(betaLG) homozygotes is equivalent to that of the endogenous PLC-beta1 mRNA in nontransgenic animals, which is reported for the first time in this species, but expression levels are significantly reduced. Although the hybrid PLCbeta1-betaLG mRNA contains all the essential information to produce a PLCbeta1 protein that could be activated, this protein was not detected by Western blot. The PLC-beta1(betaLG) mouse model described here represents a useful tool to investigate the role of the PLC-beta1 gene in the molecular mechanisms underlying growth and fertility.