|ZFIN ID: ZDB-FIG-140404-3|
|Stage Range:||Prim-5 to Long-pec|
|Stage Range:||Prim-5 to Days 45-89|
Fig. 1 lev zebrafish mutant alleles disrupt the col8a1a gene. (A) Representative col8a1a (e.g. levm531-/-) mutant embryo displaying kinking of the notochord (red arrowhead) and shortened body axis at 1 dpf. (B) Representative homozygous col8a1a mutant adult (e.g. levvu41-/-) displays shortened body axis. (C) The levvu41 lesion was meiotically mapped to a region of chromosome 9 between the markers z13213 and z34459 (number of recombinants are noted at each region) and was most highly associated with the SNP, rs40743937 in our bulk segregant analysis. According to the ensemble map (ZV9), 32 genes are located within this critical region flanked by the SSLP markers, including the col8a1a. (D–E′) col8a1a in situ hybridization at 1dpf (D and D′) showing robust expression in several midline structures at 1dpf including the floor plate, chordamesoderm/notochord, and hypochord. At 2dpf (E and E′), the expression is specific to the large vacuolated cells. (F) Structure of the predicted 711-amino acid zebrafish Col8a1a protein. The N-terminal NC2 domain and C-terminal NC1 domain flank the more-canonical collagenous domain. The NC2 domain is thought to be a propeptide domain lost during maturation, whereas the collagenous and NC1 domains are important for trimerization and supermolecular network formation respectively. The G309E (levm531) and G365S (levvu105) substitutions are located within the collagenous domain (gray box); the 607 nonsense mutation (levvu41) resides just N-terminal to the NC1 domain and the previously described gulm208a mutation.
|col8a1a||WT||standard conditions||Prim-5||floor plate||ISH|
|Long-pec||notochord inner cell||ISH|
|col8a1am531/m531||standard conditions||Prim-5||notochord kinked, abnormal|
|Prim-5||whole organism axis shortened, abnormal|
|col8a1avu41/vu41||standard conditions||Days 45-89||whole organism axis shortened, abnormal|
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Reprinted from Developmental Biology, 386(1), Gray, R.S., Wilm, T.P., Smith, J., Bagnat, M., Dale, R.M., Topczewski, J., Johnson, S.L., and Solnica-Krezel, L., Loss of col8a1a function during zebrafish embryogenesis results in congenital vertebral malformations, 72-85, Copyright (2014) with permission from Elsevier. Full text @ Dev. Biol.