LAMA3

Official Full Name

laminin subunit alpha 3

Organism

Homo sapiens

Gene ID

3909

Background

The protein encoded by this gene belongs to the laminin family of secreted molecules. Laminins are heterotrimeric molecules that consist of alpha, beta, and gamma subunits that assemble through a coiled-coil domain. Laminins are essential for formation and function of the basement membrane and have additional functions in regulating cell migration and mechanical signal transduction. This gene encodes an alpha subunit and is responsive to several epithelial-mesenchymal regulators including keratinocyte growth factor, epidermal growth factor and insulin-like growth factor. Mutations in this gene have been identified as the cause of Herlitz type junctional epidermolysis bullosa and laryngoonychocutaneous syndrome. Alternative splicing and alternative promoter usage result in multiple transcript variants. [provided by RefSeq, Dec 2014]

Synonyms

E170; LOCS; BM600; JEB2A; JEB2B; JEB2C; LAMNA

Cat.No.	Product Name	Price
CSC-DC008522	Panoply™ Human LAMA3 Knockdown Stable Cell Line	Inquiry
CSC-SC008522	Panoply™ Human LAMA3 Over-expressing Stable Cell Line	Inquiry
CSC-RT2433	Human LAMA3 Knockout Cell Line-Hela	Inquiry

Cat.No.	Product Name	Price
AD08992Z	Human LAMA3 adenoviral particles	Inquiry
LV16727L	human LAMA3 (NM_001127717) lentivirus particles	Inquiry
LV16728L	human LAMA3 (NM_198129) lentivirus particles	Inquiry
LV16729L	human LAMA3 (NM_000227) lentivirus particles	Inquiry
LV16730L	human LAMA3 (NM_001127718) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH141353	shRNA set against Human LAMA3(NM_198129.1)	Inquiry
SHH141355	shRNA set against Mouse Lama3(NM_010680.1)	Inquiry
SHH328223	shRNA set against Human LAMA3 (NM_000227.3)	Inquiry
SHH328227	shRNA set against Mouse LAMA3 (NM_010680.1)	Inquiry

Cat.No.	Product Name	Price
CDFG012549	Human LAMA3 cDNA Clone(NM_198129.1)	Inquiry
CDFH010170	Human LAMA3 cDNA Clone(NM_001127717.1)	Inquiry
CDFH010171	Human LAMA3 cDNA Clone(NM_001127718.1)	Inquiry
CDFL006805	Mouse Lama3 cDNA Clone(NM_010680.1)	Inquiry
MiUTR1H-05558	LAMA3 miRNA 3'UTR clone	Inquiry
MiUTR1M-06511	LAMA3 miRNA 3'UTR clone	Inquiry
MiUTR3H-03636	LAMA3 miRNA 3'UTR clone	Inquiry
MiUTR3H-03637	LAMA3 miRNA 3'UTR clone	Inquiry
MiUTR3H-03638	LAMA3 miRNA 3'UTR clone	Inquiry
CDCB189683	Rabbit LAMA3 ORF clone (XM_008261146.1)	Inquiry
CDCL126069	Mouse LAMA3 ORF clone (NM_001127718.1)	Inquiry
CDCR249123	Mouse Lama3 ORF Clone(NM_010680.1)	Inquiry
CDCR325501	Human LAMA3 ORF Clone(NM_198129.1)	Inquiry
CDCR348901	Human LAMA3 ORF Clone(NM_001127717.1)	Inquiry

Detailed Information

Recent Progress

Laminin is a series of heterotrimeric proteins that contain alpha, beta and gamma subunits, assembling through a coiled domain. Laminin is the main components of basement membrane, with additional functions in tumor invasion and metastasis, along with cell migration regulation and mechanical signal transduction. In particular, The Lama3 gene codes laminin alpha3 chain which interacts with beta3 and gamma2 chains to form laminin-332, the most abundant laminin heterotrimer in the basal lamina of skin and mucosa, and is also strongly associated with cancer.

It has been indicated by genetic, clinical, and biochemical studies that to maintain the integrity of the dermal-epidermal junction, the subset of laminins that contain the chain encoded by the Lama3 gene are required. Consequently, inherited mutations or constitutive mutations in the mouse gene prevent expression of these laminins, causing junctional epidermolysis bullosa (JEB), which is a very severe and often lethal disorder characterized by detachment of the epidermis from the dermis (Fig.1). To further identify the relationship between the Lama3 gene and the disease, researchers disrupted the Lama3 gene in basal keratinocytes of adult mice, which led to the disappearance of chain-containing laminins at the dermal-epidermal junction along with formation of subepidermal blisters. The mice suffered from loss of nails, erosions on the footpads, inflammation, and development of skin fibrosis with extensive accumulation of interstitial and microfibrillar collagens. This sheds light on the possible relationship between the Lama3 gene and the disease.

Fig. 1. Junctional blisters and laminin expression in mutant skin. (C) A junctional blister present in the mutant skin that is characterized by a separation of the epidermis (e) from the dermis (d) at the BMZ. Basal cells in the lesion appear sparse and flattened (arrows). Arrows with asterisks mark cell clusters that appear undifferentiated in the superbasal cell layer. (MC Ryan et al, 2016)

While examining pedigrees of JEB patients with LAMA3 mutations, investigators observed that heterozygous carriers of functional null mutations presented subtle enamel pitting in the absence of skin fragility or other JEB symptoms. At the case report, two new LAMA3 functional null mutations were introduced: nonsense c.2377C>T p.(Arg793Ter) and splice-site c.4684+1G>A mutation which was in the heterozygous carriers exhibiting enamel pitting. It was also discovered that both parents had offspring inflicted with JEB and displayed subtle enamel pitting of secondary dentition without any sign of skin blistering. The mentioned enamel abnormality in LAMA3 mutation carriers could be attributed to a half dose effect of the laminin chain (haploinsufficiency).

Researchers also created an inducible transgenic mouse model (Lama3fl/fl/K14-Cre-ERT mouse), in which the Lama3 gene is turned off at certain time point in basal keratinocytes of the skin and mucosae. Compare to those models constantly lacking laminin-332 with early lethality, the transgenic model is viable, also allowing researchers to examine the molecular and cellular consequences caused by the loss of the laminin alpha3 chain.

Similar to the junctional epithelium, the peri-implant epithelium attaches to the surface of the implant via hemi-desmosomes (HDs) and internal basal lamina which is the extracellular matrix containing laminin332. Through layer-by-layer assembly and antibody-antigen specific binding for substrate-mediated gene transduction, researchers were able to produce a multilayer coating modified with the Lama3 on the titanium implant surface. The results in vitro indicated that the LAMA3-modified coating on the titanium surface could improve cell adhension in the early stage, and facilitate the expression of laminin α3 on both the protein and the gene levels. Also, the formation of hemidesmosomes at the interface became prominent. In vivo experiments demonstrated that the LAMA3 gene coating on the implant surface could enhance the expression of laminin α3 and improve the biological sealing between the implant and the epithelium. These findings in improving biological sealing between titanium implant and gingival epithelium offer a new approach and experimental evidence for research on the interface of the implant and soft tissues.

References:

Xiao-Dong, H. U., Yang, Y. X., & Gastroenterology, D. O. (2016). “Progress of the relationship between lama3 gene and cancer”. Journal of Chinese Practical Diagnosis & Therapy.
Pesch, M., König, S., & Aumailley, M. (2017). “Targeted disruption of the lama3 gene in adult mice is sufficient to induce skin inflammation and fibrosis”. Journal of Investigative Dermatology, 137(2), 332-340.
Gostyńska KB, Yan Yuen W, Pasmooij AM, Stellingsma C, Pas HH, & Lemmink H, et al. (2016). “Carriers with functional null mutations in lama3 have localized enamel abnormalities due to haploinsufficiency”. European Journal of Human Genetics Ejhg, 25(1), 94.
Aumailley, M., Koenig, S., Sasaki, T., & Pesch, M. (2016). “Inducible basal keratinocyte-specific knockout of the lama3 gene: a model for wound healing and fibrosis?”. Journal of Dermatological Science, 84(1), e145-e145.
Zhang, J., Wang, H., Wang, Y., Dong, W., Jiang, Z., & Yang, G. (2017). “Substrate-mediated gene transduction of lama3 for promoting biological sealing between titanium surface and gingival epithelium”. Colloids & Surfaces Biointerfaces, 161, 314.

Quick Inquiry

LAMA3

You might be looking for:

Detailed Information