Fibrillin-2^Mp aggregated into large intracellular inclusions within the rough endoplasmic reticulum.

<p>(A–B) Whole Mount <i>In Situ Hybridisation</i> to <i>Fbn2</i> using antisense 3′-UTR riboprobes of <i>Fbn2</i> for Wt and <i>Isoc1</i> for <i>Mp/Mp</i> in early Wt and <i>Mp/Mp</i> embryos (E11.5) revealed the spaciotemporal expression of the variant <i>Fbn2</i> alleles appeared unaffected by the genomic inversion and that <i>cis</i>-regulation of the genes was unchanged. <i>Fbn2</i> was expressed in the developing eyes (arrows), limbs (arrowheads), and tail (asterisks), and expression was also observed in the somites. (C–D) Section <i>In Situ Hybridisation</i> for <i>Fbn2</i> at E13.5 again showed that mutant <i>Fbn2</i> expression was comparable to Wt in the eyes, with <i>Fbn2</i> identified in the periocular (m) and corneal (c) mesenchyme, and faintly in the anterior retina (arrows). No expression was identified in the lens (ln). Scale bars in, 100 µm. (E–F) Immunohistochemical analysis of the anterior region of E13.5 Wt eyes illustrated that Fibrillin-2 was localised to extracellular regions in the corneal mesenchyme and in the region of apposition between the lens and neural retina (arrowheads). In contrast, Fibrillin-2^Mp in <i>Mp/Mp</i> eyes was not observed in these extracellular locations but instead appeared to be retained within cells throughout the developing eye, with the anterior neural retina (arrows) and adjacent RPE displaying the most numbers of positive-cells. Scale bars, 50 µm.