Introduction to the mouse as a model for studying basement membranes
The mouse has long served as a valuable experimental in vivo model to investigate many aspects of development, physiology and diseases. Human and mouse have a common ancestor, hence, they share virtually the same set of functional genes and a wide range of well-conserved signaling pathways, molecular and cellular functions, in addition to physiological and pathological processes.
Mice are advantageous in their ability to allow gene manipulation (deletion, mutation, insertion, transgene) to define and/or test the function of target genes in different biological contexts (health, disease and embryonic differentiation) at a system-based level and test therapeutic approaches in vivo. Currently, there are several wild-type and genetically engineered mouse strains available, and most of these are relatively easy to breed and manipulate within the lab. Given their small size and relatively short developmental timeframe, mouse colonies can be raised quickly and kept, thus enabling large scale/high throughput studies.
Over the past 5 decades, the use of mouse models has contributed tremendously to determine:
- the molecular composition of basement membranes throughout different tissues/organs via antibody-based approaches, enrichment strategies and further employment of global omics tools (such as transcriptomics and proteomics);
- ultrastructure of basement membranes via electronic microscopy;
- the nanoscale topological distribution of its major components using fluorescent antibodies and super-resolution microscopy. Moreover, mouse models of genetic diseases affecting basement membranes (e.g., Alport syndrome, Pierson syndrome, congenital muscular dystrophy) have been successfully employed to elucidate the pathological underpinnings that cause abnormalities in basement membranes and cell-matrix interactions in disease.
Labs focusing on basement membrane research
Lennon Lab: Collagen IV and Alport syndrome
Miner Lab: Collagen IV and laminin disorders
Pihlajaniemi Lab: Collagen XVIII disorders
Sorokin Lab: Laminins and endothelial function
Van Agtmael Lab: Type IV collagen disorders
Hamill Lab: Laminins and LaNts
Nystroem Lab: Skin disorders and collagen VII
- Nanoscale protein architecture of the kidney glomerular basement membrane. Suleiman, H et al. Elife. 2013 Oct 8. PMID: 24137544
- Molecular and functional defects in kidneys of mice lacking collagen alpha 3(IV): implications for Alport syndrome. Miner, JH and Sanes JR. J Cell Biol. 1996 Dec. PMID: 8947561
- Proteinuria precedes podocyte abnormalities inLamb2-/- mice, implicating the glomerular basement membrane as an albumin barrier. Jarad, G et al. J Clin Invest. 2006 Aug. PMID: 16886065
- Linker proteins restore basement membrane and correct LAMA2-related muscular dystrophy in mice. Reinhard, JR et al. Sci Transl Med. 2017 Jun 28. PMID: 28659438
- Laminin alpha2 deficiency and muscular dystrophy; genotype-phenotype correlation in mutant mice. Guo, LT et al. Neuromuscul Disord. 2003 Mar. PMID: 12609502