The Lrp4 hypomorphic allele (Lrp4ECD, Lrp4 EC STOP, Lrp4<sup>hypo</sup>, Megf7<sup>-</sup>, Lrp4STOP1723) contains a premature stop codon within the exon immediately upstream of the transmembrane segment. Much of the targeted exon and 3' adjacent intron is absent. No functional full-length transcripts are detected in brain tissue. The transcript generated is out of frame beyond the sequences coding for the transmembrane segment, which results in a truncated protein with loss of the transmembrane and intracellular domains of the LRP4 protein.  While the LRP4 extracellular domain (ECD) is expressed normally, the lack of a membrane anchor leads to shedding/secretion of the ECD into the extracellular space.  This results in diminished, but not completely absent, LRP4 interactions with its extracellular ligands (i.e., hypomorphic phenotype).  Mice homozygous for this Lrp4 hypomorphic allele are viable and fertile. Homozygous mice exhibit growth retardation, fully penetrant polysyndactyly with digit fusions, abnormal tooth development and changes in Shh- and Wnt-signaling.  The tooth development abnormalities include supernumerary incisors/molars of reduced size and abnormal shape, and incisors with grooved enamel surfaces that exhibit the same molecular characteristics as the tips of molar cusps. Homozygous mice also have defects in neuromuscular junction development, and bone growth and turnover. These mutant mice may be useful in studying the LRP4 extracellular domain in embryonic development (polysyndactyly, tooth, neuromuscular junction), as well as low-density lipoprotein (LDL) receptor family-, Shh-, Bmp-, and Wnt-signaling pathways. 

These Lrp4ECD mice harbor a hypomorphic allele of the low density lipoprotein receptor-related protein 4 locus that results in a truncated protein with loss of the transmembrane and intracellular domains of the LRP4 protein. The LRP4 extracellular domain (ECD) is expressed normally and secreted into the extracellular space; resulting in diminished, but not completely absent, LRP4 interactions with its extracellular ligands.  These Lrp4ECD mice may be useful in studying the LRP4 extracellular domain in embryonic development (polysyndactyly, tooth, neuromuscular junction), as well as low-density lipoprotein (LDL) receptor family-, Shh-, Bmp-, and Wnt-signaling pathways.

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