Col11a1 and Col11a2 mRNA expression in the developing mouse cochlea: implications for the correlation of hearing loss phenotype with mutant type XI collagen genotype.
OBJECTIVE
Mutations in the fibrillar collagen genes COL11A1 and COL11A2 can cause sensorineural hearing loss associated with Stickler syndrome. There is a correlation of hearing loss severity, onset, progression and affected frequencies with the underlying mutated collagen gene. We sought to determine whether differences in spatial or temporal expression of these genes underlie this correlation, and to identify the cochlear cell populations expressing these genes and the structures likely to be affected by mutations.


METHODS
We used in situ hybridization analysis of C57BL/6J mouse temporal bones.


RESULTS
Similar, diffuse expression of Col11a1 and Col11a2 mRNA was first observed in the cochlear duct at embryonic Day 15.5, with increasingly focal hybridization being noted at postnatal Days 1 and 5 in the greater epithelial ridge and lateral wall of the cochlea. The greater epithelial ridge appeared to be the main, if not only, source of mRNA encoding Col11a1 and Col11a2 in the tectorial membrane. At postnatal Day 13, Col11a1 and Col11a2 expression became more focal and co-localized in the inner sulcus, Claudius' cells and cells of Boettcher.


CONCLUSIONS
We did not observe spatial or temporal differences in mRNA expression that could account for the auditory phenotype genotype correlation. The expression patterns suggest essential roles for Col11a1 and Col11a2 in the basilar or tectorial membranes.
Shpargel
Karl B
KB
Section on Gene Structure and Function, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Rockville, MD, USA.
Makishima
Tomoko
T
Griffith
Andrew J
AJ
D000818:Animals; D001489:Basilar Membrane / Q000196:embryology / Q000502:physiology; D003051:Cochlea / Q000196:embryology / Q000502:physiology*; D024161:Collagen Type XI / Q000235:genetics* / Q000378:metabolism; D005109:Extracellular Matrix / Q000502:physiology; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D017403:In Situ Hybridization; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010641:Phenotype; D012333:RNA, Messenger / Q000096:biosynthesis*; D012044:Regression Analysis; D013680:Tectorial Membrane / Q000196:embryology / Q000502:physiology
D024161:Collagen Type XI; D012333:RNA, Messenger