In the BALB.LDLR-/- strain, a neomycin (neo) selection cassette is inserted in exon 4 of the low density lipoprotein receptor (Ldlr) gene, abolishing endogenous gene function. Homozygous mice are viable, fertile, appear normal in size, and do not display any gross physical or behavioral abnormalities. On a 4% diet, BALB.LDLR-/- mice have increased cholesterol (~200 mg/dl), increased triglycerides (~170mg/dl), and increased blood glucose (122 mg/dl) as compared with wildtype (WT). When moved onto a 21% fat diet these mice have cholesterol levels of 572 mg/dl, triglyceride levels of 180mg/dl, and blood glucose levels of 141 mg/dl. They exhibit renal injury, tubulointerstitial injury, and an increase in interstitial macrophages, and an increase in blood urea nitrogen when challenged with hyperlipidemia and hyperglycemia. When injected with Streptozotocin these mice also exhibit atherosclerotic lesions, aortic sinus lesions, and aortic fatty streak lesions caused by hyperlipidemia. These mice may be useful for studying the effects of hyperlipidemia and hyperglycemia on diabetic nephrology and artherosclerosis.
