Disruption of the mouse phospholipase C-β1 gene in a β-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 β-lactoglobulin (βLG) 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 βLG transgene are inserted in an intronic region of the phospholipase C-β1 (PLC-β1) gene, which plays a pivotal role in modulating different cellular functions. As a result of the insertional mutation (PLC-β1βLG mutation), a hybrid messenger RNA (mRNA) between the mouse PLC-β1 and the goat βLG genes is transcribed. The tissue-specific pattern of expression of this hybrid mRNA in PLC-β1βLG homozygotes is equivalent to that of the endogenous PLC-β1 mRNA in nontransgenic animals, which is reported for the first time in this species, but expression levels are significantly reduced. Although the hybrid PLCβ1-βLG mRNA contains all the essential information to produce a PLCβ1 protein that could be activated, this protein was not detected by Western blot. The PLC-β1βLG mouse model described here represents a useful tool to investigate the role of the PLC-β1 gene in the molecular mechanisms underlying growth and fertility. © 2004 Elsevier B.V. All rights reserved.