Phenotype Image Detail

Image

Caption

Neuroanatomical, opthalmic, and auditory phenotypes of Nipbl^{Gt(RRS564)Byg}/Nipbl⁺ mice. (A) Measurements from micro-CT analysis reveal a 25% reduction in endocranial volume in Nipbl^{Gt(RRS564)Byg}/Nipbl⁺ (+/-) mice (data are means +/-SD from 40 wild-type and 23 mutant skulls). (B) Nissl-stained cornal sections of adult wild-type (+/+) and mutant brains illustrate reduced brain size, but grossly normal neuroanatomy. MHb, medial habenular nucleus; fr, fasiculus retroflexus; mt, mammilothalamic tract; dg, dentate gyrus; cc, corpus callosum. Scale bar: 1 mm. (C) Cerebellar hypoplasia in mutant mice. Cresyl violet-stained midsagittal sections through the cerebellum of adult wild-type and mutant mice. Mutant cerebella are smaller overall, with a less well-developed folium IX (bracket); note the subfolium (arrow in +/+) that was missing in 100% of analyzed mutants (asterisk; N = 3 mutant and 3 wild-type littermate controls assessed). Reduction in the size of folium I was also commonly observed in mutants (not shown). Scale bar: 500 um. (D,E) Corneal pathology in mutant mice. (D) External view of wild-type and mutant eyes, demonstrating central opacity (green arrowhead) and swelling/inflammation in the periorbital area (arrows) in the mutant. (E) Sections through wild-type and mutant eyes, demonstrating disruption of corneal structure in the mutant, including infiltration of cells into the stroma and loss of epithelium. Ocular opacification was observed in 14% (24/173) of post-weaning mice tested. Scale bar: 100 um. (F,G) Hearing deficits in mutants. (F) Auditory brainstem evoked response (ABR) records for a pair of wild-type and mutant littermates. Stacked curves are responses to successive 10 dB increments of a pure-tone stimulus, and display five characteristic peaks of differing latency. In the mutant curves, hearing loss is indicated by the much higher response threshold (this is seen in less than half of mutants). (G) Average background-subtracted sizes of Peaks II, III, and IV (normalized to Peak I to correct for experimental variation due to differences in electrode placement) for the 90 dB tone response of 6 wild-type and 6 mutant mice. Mutants show marked depression of peak III (P<0.02, ANOVA), consistent with abnormalities at the level of the auditory nerve or brainstem.

Copyright

This image is from Kawauchi S, PLoS Genet 2009 Sep;5(9):e1000650, and is displayed under the terms of the Creative Commons Attribution 4.0 International License. J:154117

Associated Alleles

Symbol	Name
Nipbl^Gt(RRS564)Byg	NIPBL cohesin loading factor; gene trap RRS564, BayGenomics

Associated Genotypes

Allelic Composition	Genetic Background
Nipbl^Gt(RRS564)Byg/Nipbl^+	involves: 129P2/OlaHsd * CD-1
Nipbl^Gt(RRS564)Byg/Nipbl^+	involves: 129P2/OlaHsd