Disease relevance of LAMC1

• Localized and generalized Mitis types as well as the majority of tested families with the Herlitz type of junctional epidermolysis bullosa appeared not to be similarly linked or associated to LAMC1 [1].
• The exon-intron structure of the human laminin B2 chain gene was elucidated from genomic lambda phage clones spanning 2 kilobase pairs (kb) of the 5'-flanking region, 58 kb of the structural gene and 10 kb of the 3'-flanking region [2].
• Sequence variant in the laminin gamma1 (LAMC1) gene associated with familial pelvic organ prolapse [3].

High impact information on LAMC1

• Absence of basement membranes after targeting the LAMC1 gene results in embryonic lethality due to failure of endoderm differentiation [4].
• The LAMC1 gene coding for the laminin gamma1 subunit was targeted by homologous recombination in mouse embryonic stem cells [4].
• The gene for the laminin B2t chain (LAMB2T) was localized to chromosome 1q25-q31 in close proximity to the laminin B2 chain gene [5].
• Comparison of the amino acid sequences showed that the novel laminin chain is homologous to the laminin B2 chain [5].
• By in situ hybridization expression of the B2t chain was localized to specific epithelial cells in skin, lung, and kidney as opposed to a general epithelial and endothelial cell expression of the laminin B2 chain in the same tissues [5].

Biological context of LAMC1

• The four patients of these families are all homozygous for the 146 bp LAMC1 allele present only on 5% of random Norwegian chromosomes [1].
• The LAMC2 gene contains 23 exons and is structurally highly homologous with the 28-exon LAMC1 gene (Kallunki et al., 1991, J. Biol. Chem. 266: 221-228), with 16 exons having identical sizes in the two genes [6].
• Of the genes confirmed to be expressed, LAMC1 was further evaluated by sequencing and select single nucleotide polymorphism (SNP) genotyping for causative sequence variants in affected family members [3].
• Three informative families show a lod score of +1.65 at zero recombination to a trinucleotide repeat marker in intron 20 of the laminin gamma 1 (LAMC1, previously LAMB2) locus on 1q31 [1].
• A laminin B2 chain cDNA clone was isolated from a human lung cDNA library by screening with antibody against mouse laminin [7].

Anatomical context of LAMC1

• The human laminin B2 gene (LAMB2) was assigned to region 1q25----q31 by (1) hybridization of the probe to DNA from a panel of human x mouse somatic cell hybrids containing different human chromosomes and (2) in situ hybridization to isolated metaphase chromosomes [8].
• Treatment of mesangial cells with either phorbol 12-myristate 13-acetate (PMA) or interleukin-1beta induces an increase in laminin B2 chain mRNA levels [9].

Associations of LAMC1 with chemical compounds

• The 100-kDa chain of nicein/kalinin is a laminin B2 chain variant [10].

Other interactions of LAMC1

• The candidate genes LAMC1, NPR1, and CNR2 were excluded from the region by linkage [11].
• Structure of the human laminin B2 chain gene reveals extensive divergence from the laminin B1 chain gene [2].
• Products from the proteolytic cleavage of the A and B2 chains of laminin were observed with the sites of cleavage determined to be at position 2666 in the laminin A chain and position 1238 in the laminin B2 chain [12].
• Using GATA6 transformed Lamc1-null endoderm-like cells, we demonstrate that laminin 1 exhibited by the basement membrane induces epiblast differentiation and cavitation by cell-to-matrix/matrix-to-cell interactions that are similar to the in vivo crosstalk in the early embryo [13].

References