Generation of a conditionally null allele of the laminin α1 gene

Alpy, Fabien; Jivkov, I.; Sorokin, Lydia; Klein, Albrecht; Arnold, Christiane; Huss, Y.; Kédinger, Michèle; Simon‐Assmann, Patricia

doi:10.1002/gene.20154

Cited by 57 publications

(51 citation statements)

References 50 publications

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“…RM serves as a barrier between the maternal blood and the developing embryo, and also as a facilitator of materno-embryonic exchange of nutrients and gases (Williamson et al, 1997). Mutation in any of the LAMININ-1 subunit genes results in the absence of RM Alpy et al, 2005). Our results indicated that the RM was intact in Ric-8 À/À embryos.…”

Section: Ric-8 2/2 Embryos Are Not Competent In Organogenesismentioning

confidence: 64%

Nucleotide exchange factor RIC‐8 is indispensable in mammalian early development

Tõnissoo¹,

Lulla²,

Meier³

et al. 2010

Developmental Dynamics

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The guanine nucleotide exchange factor RIC-8 is a conserved protein essential for the asymmetric division in the early embryogenesis in different organisms. The function of RIC-8 in mammalian development is not characterized so far. In this study we map the expression of RIC-8 during the early development of mouse. To elucidate the RIC-8 function we used Ric-8 2/2 mutant embryos. The Ric-8 2/2 embryos reach the gastrulation stage but do not develop further and die at E6.5-E8.5. We characterized the Ric-8 2/2 embryonic phenotype by morphological and marker gene analyses. The gastrulation is initiated in Ric-8 2/2 embryos but their growth is retarded, epiblast and mesoderm disorganized. Additionally, the basement membrane is defective, amnion folding and the formation of allantois are interfered, also the cavitation. Furthermore, the orientation of the Ric-8 2/2 embryo in the uterus was abnormal. Our study reveals that the activity of RIC-8 protein is irreplaceable for the correct gastrulation of mouse embryo. Developmental Dynamics 239:3404-3415,

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Section: Ric-8 2/2 Embryos Are Not Competent In Organogenesismentioning

confidence: 64%

Nucleotide exchange factor RIC‐8 is indispensable in mammalian early development

Tõnissoo¹,

Lulla²,

Meier³

et al. 2010

Developmental Dynamics

View full text Add to dashboard Cite

show abstract

“…For example, genetically eliminating any subunit of the most abundant laminin heterotrimer during mouse embryogenesis (a1b1c1) results in endoderm differentiation defects, widespread apoptosis and embryonic lethality (Alpy et al, 2005;Miner et al, 2004;Smyth et al, 1999). In addition, mice lacking the a5 laminin subunit do not survive until birth, and have prenatal defects in digit separation, glomerulogenesis and neural tube closure (Kikkawa et al, 2003;Miner et al, 1998;Nguyen et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

An active role for basement membrane assembly and modification in tissue sculpting

Morrissey

Sherwood

2015

Journal of Cell Science

113

105

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Basement membranes are a dense, sheet-like form of extracellular matrix (ECM) that underlie epithelia and endothelia, and surround muscle, fat and Schwann cells. Basement membranes separate tissues and protect them from mechanical stress. Although traditionally thought of as a static support structure, a growing body of evidence suggests that dynamic basement membrane deposition and modification instructs coordinated cellular behaviors and acts mechanically to sculpt tissues. In this Commentary, we highlight recent studies that support the idea that far from being a passive matrix, basement membranes play formative roles in shaping tissues.

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“…Furthermore, the gene encoding laminin ␣1, LAMA1, and several peptides derived from laminin ␣1 have been shown to induce angiogenic sprouting in cell culture and angiogenesis in chicken chorioallantoic membrane assays (8,9). It has been difficult to study the functional role of this gene beyond embryogenesis, because all Lama1 mouse mutants generated to date die by embryonic day 7 (10,11). Mutant zebrafish, however, have provided some insights into the function of lama1 (12)(13)(14)(15)(16).…”

mentioning

confidence: 99%

Mutations in Lama1 Disrupt Retinal Vascular Development and Inner Limiting Membrane Formation

Edwards

Mammadova‐Bach

Alpy

et al. 2010

Journal of Biological Chemistry

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The Neuromutagenesis Facility at the Jackson Laboratory generated a mouse model of retinal vasculopathy, nmf223, which is characterized clinically by vitreal fibroplasia and vessel tortuosity. nmf223 homozygotes also have reduced electroretinogram responses, which are coupled histologically with a thinning of the inner nuclear layer. The nmf223 locus was mapped to chromosome 17, and a missense mutation was identified in Lama1 that leads to the substitution of cysteine for a tyrosine at amino acid 265 of laminin ␣1, a basement membrane protein.Despite normal localization of laminin ␣1 and other components of the inner limiting membrane, a reduced integrity of this structure was suggested by ectopic cells and blood vessels within the vitreous. Immunohistochemical characterization of nmf223 homozygous retinas demonstrated the abnormal migration of retinal astrocytes into the vitreous along with the persistence of hyaloid vasculature. The Y265C mutation significantly reduced laminin N-terminal domain (LN) interactions in a bacterial twohybrid system. Therefore, this mutation could affect interactions between laminin ␣1 and other laminin chains. To expand upon these findings, a Lama1 null mutant, Lama1 tm1.1Olf , was generated that exhibits a similar but more severe retinal phenotype than that seen in nmf223 homozygotes. The increased severity of the Lama1 null mutant phenotype is probably due to the complete loss of the inner limiting membrane in these mice. This first report of viable Lama1 mouse mutants emphasizes the importance of this gene in retinal development. The data presented herein suggest that hypomorphic mutations in human LAMA1 could lead to retinal disease.

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Generation of a conditionally null allele of the laminin α1 gene

Cited by 57 publications

References 50 publications

Nucleotide exchange factor RIC‐8 is indispensable in mammalian early development

Nucleotide exchange factor RIC‐8 is indispensable in mammalian early development

An active role for basement membrane assembly and modification in tissue sculpting

Mutations in Lama1 Disrupt Retinal Vascular Development and Inner Limiting Membrane Formation

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