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1(IV) Collagen Mutations in
Caenorhabditis elegans and the Effects of 1 and 2(IV)
Mutations on Type IV Collagen Distribution
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611
Type IV collagen is a major component of
basement membranes. We have characterized 11 mutations in emb-9, the 
1(IV) collagen gene of Caenorhabditis elegans, that result in a spectrum of phenotypes. Five are substitutions of glycines in the Gly-X-Y domain and cause semidominant, temperature-sensitive
lethality at the twofold stage of embryogenesis. One is a
glycine substitution that causes recessive, non-temperature-sensitive larval lethality. Three putative null alleles, two nonsense mutations and a deletion, all cause
recessive, non-temperature-sensitive lethality at the
threefold stage of embryogenesis. The less severe null
phenotype indicates that glycine substitution containing mutant chains dominantly interfere with the function of other molecules. The emb-9 null mutants do not stain with anti-EMB-9 antisera and show intracellular
accumulation of the 2(IV) chain, LET-2, indicating
that LET-2 assembly and/or secretion requires EMB-9.
Glycine substitutions in either EMB-9 or LET-2 cause
intracellular accumulation of both chains. The degree
of intracellular accumulation differs depending on the allele and temperature and correlates with the severity
of the phenotype. Temperature sensitivity appears to
result from reduced assembly/secretion of type IV collagen, not defective function in the basement membrane. Because the dominant interference of glycine
substitution mutations is maximal when type IV collagen secretion is totally blocked, this interference appears to occur intracellularly, rather than in the basement membrane. We suggest that the nature of
dominant interference caused by mutations in type IV
collagen is different than that caused by mutations in fibrillar collagens.
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