May 2008
Volume 49, Issue 13
ARVO Annual Meeting Abstract  |   May 2008
Targeted Disruption of the WD Repeat Domain 36 Gene (WDR36) in Mutant Mice
Author Affiliations & Notes
  • M. Kroeber
    Human Anatomy & Embryology, University of Regensburg, Regensburg, Germany
  • L. Maerz
    Human Anatomy & Embryology, University of Regensburg, Regensburg, Germany
  • M. R. Bösl
    Max Planck Institute of Neurobiology, Martinsried, Germany
  • M. Wegner
    Institute of Biochemistry, University of Erlangen-Nürnberg, Erlangen, Germany
  • E. R. Tamm
    Human Anatomy & Embryology, University of Regensburg, Regensburg, Germany
  • Footnotes
    Commercial Relationships  M. Kroeber, None; L. Maerz, None; M.R. Bösl, None; M. Wegner, None; E.R. Tamm, None.
  • Footnotes
    Support  Supported by DFG grant Ta 115/15-1.
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5116. doi:
  • Views
  • Share
  • Tools
    • Alerts
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      M. Kroeber, L. Maerz, M. R. Bösl, M. Wegner, E. R. Tamm; Targeted Disruption of the WD Repeat Domain 36 Gene (WDR36) in Mutant Mice. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5116. doi:

      Download citation file:

      © ARVO (1962-2015); The Authors (2016-present)

  • Supplements

Purpose: : Mutations in WDR36 (WD repeat domain 36) have been identified as causative for GLC1G-linked open-angle glaucoma (Monemi at al., HMG 2005). WDR36 has been highly conserved throughout mammalian evolution and encodes for WD repeat domain 36 protein, a 951 aa protein that is characterized by multiple G-beta WD40 repeats and an UTP21-domain. A homologue in yeast, Utp21, is part of the small-subunit processome with putative roles in both pre-rRNA processing and ribosome assembly. To identify the molecular functions of WDR36 in mammals, we generated mice with a targeted disruption of Wdr36.

Methods: : The genomic sequence for the Wdr36 locus of 129/Sv mice was obtained by PCR. A 2.0 kb fragment immediately upstream of the translation start was used as 5’-homology region. The start codon of the beta-galactosidase marker (LacZ) was placed exactly over the start codon. A 4.2 kb fragment starting 19.3 kb downstream of the open reading frame was used as 3’-homology region. Homologous recombination resulted in deletion of the start ATG and the first 16 exons. The deleted genomic region was replaced with a lacZ-floxed pgk-neomycin cassette. For negative selection, a hsv-tk cassette was placed outside the 5`-homology region. Genotyping was performed by southern hybridization of ES cells. Eyes of heterozygous (+/-) animals up to one year of age were investigated by light and electron microscopy. Intraocular pressure (IOP) was measured using a TonoLab tonometer. The total number of optic nerve axons was counted on cross sections.

Results: : Mice heterozygous (+/-) for the null mutation are viable and fertile whereas homozygous (-/-) mice die prior to embryonic day 9.5. Real-time RT-PCR and northern blot analysis demonstrated a substantial reduction of Wdr36 mRNA in +/- mice as compared to wild-type (+/+) littermates. The eyes of +/- mice did not show any structural alterations within trabecular meshwork and optic nerve head when examined by light and electron microscopy. No significant differences in IOP or obvious changes in the number of optic nerve axons were found between +/- and wildtype mice at one year of age.

Conclusions: : The lack of a discernable phenotype in Wdr36-heterozygous mutant mice suggests that haploinsufficiency of WDR36 is not a critical mechanism for development of POAG.

Keywords: transgenics/knock-outs • genetics • pathology: experimental 

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.