Lrp5 point mutation underlies retinal dysfunction in Tvrm111B mutant mice

Abstract

Purpose: On an ERG screen of ENU-mutagenized C57BL/6J mice, the Tvrm111B mutant was identified due to a reduced amplitude b-wave component. Here we identify the gene involved and define the retinal phenotype.

Methods: Linkage mapping was used to identify the Tvrm111B gene locus. Retinal electrophysiology was evaluated by ERG. Retinal anatomy was evaluated by optical coherence tomography, fluorescein angiography, and immunohistochemistry. Bone mineral density was measured using peripheral dual-energy X-ray absorptiometry.<br />

Results: The Tvrm111B locus mapped to a region of Chr. 19 that contains Lrp5. Subsequent sequencing identified an insertional mutation for which the functional impact is under investigation. Lrp5^tvrm111B mice have a number of vascular abnormalities affecting the deep retinal layers, delayed hyaloid regression, and leakage on fluorescein angiography. Lrp5^tvrm111B mice also have significantly decreased bone mass.

Conclusions: When compared to the phenotype of complete loss of function models for Lrp5, that of the Lrp5^tvrm111B mutant is less severe. As a result, this model expands the allelic series of Lrp5 mutants, and is available without restriction to the research community.<br />