| 14725 | A2ARV4 | LRP2_MOUSE | Low-density lipoprotein receptor-related protein 2 (LRP-2) (Glycoprotein 330) (gp330) (Megalin) | DISRUPTION PHENOTYPE | Severe facial dysgenesis and impaired forebrain development around mid-gestation, absence of Shh expression and decreased cell proliferation in the ventral neural tube, and aberrant expression of morphogens Fgf8 and Bmp4 (PubMed:15623804). Reduced expression of homeobox protein Six3 at 8.0 dpc in the prospective forebrain and impaired Shh expression at the ventral midline with resulting midline formation defects and holoprosencephaly (PubMed:22340494). At 9.5 dpc, loss of Shh in the ventral anterior diencephalon and increased Bmp4 expression in the dorsal forebrain (PubMed:22340494). Increased Bmp4 expression and impaired proliferation of neural precursor cells in the subependymal zone of the brain which results in decreased numbers of neuroblasts reaching the olfactory bulb (PubMed:20460439). Compound heterozygotes display enlarged and exophthalmic eyes with thinning of the retina (PubMed:26439398). Severe cardiovascular abnormalities including aortic arch anomalies, persistent truncus arteriosus with coronary artery anomalies, ventricular septal defects, overriding of the tricuspid valve, marked thinning of the ventricular myocardium, and abnormal positioning of the neural crest cells and second heart field (PubMed:26822476). Impaired endocytosis of folate bound to the folate receptor FOLR1, reduced folate levels in embryos and impaired closure of the rostral neural tube (PubMed:24639464). High lethality at and after birth with survivors showing profound hearing loss, elevated lipofuscin granule levels and irregular apical surfaces in marginal cells of the stria vascularis, complete loss of potassium ion channel KCQN1 in basal and midbasal cochlear turns, and reduced estrogen uptake in the stria vascularis (PubMed:17846082). Survivors also display severe vitamin D deficiency and bone formation defects (PubMed:10052453). Failure of the vaginal cavity to open after birth in females and impaired testis descent in males with the left testis poorly developed and severely retarded in size (PubMed:16143106). Conditional knockout in the kidney results in reduced expression of CUBN in kidney cells and little or no uptake of myoglobin (PubMed:12724130). It also results in reduced uptake of Cst3 by kidney proximal tubule cells (PubMed:17462596). In addition, it causes pronounced urinary excretion of Apom, Birc5/survivin, and Mmp2 together with Timp1 (PubMed:16099815, PubMed:23825075, PubMed:28659595). {ECO:0000269|PubMed:10052453, ECO:0000269|PubMed:12724130, ECO:0000269|PubMed:15623804, ECO:0000269|PubMed:16099815, ECO:0000269|PubMed:16143106, ECO:0000269|PubMed:17462596, ECO:0000269|PubMed:17846082, ECO:0000269|PubMed:20460439, ECO:0000269|PubMed:22340494, ECO:0000269|PubMed:23825075, ECO:0000269|PubMed:24639464, ECO:0000269|PubMed:26439398, ECO:0000269|PubMed:26822476, ECO:0000269|PubMed:28659595}. |