Fig. 1
From: Mutations in SMARCB1 and in other Coffin–Siris syndrome genes lead to various brain midline defects
Phenotypic and genetic analyses of mutant and control mice. a Control and mutant animal (age: 3 weeks). b Brains of 3-week-old mutant mice are smaller and their cerebral hemispheres are separated by a midline gap (arrowheads). c Summary of brain phenotypes in mutant animals. d Cerebelli of 3–4-week-old control and mutant animals; right panel: brains were ink-stained for the visualization of fissures; h cerebellar hemisphere, v cerebellar vermis. Note the smaller size and reduced foliation of mutant cerebelli. Upper panel: control brain with longitudinal (anterior-posterior) fissures (arrowheads) separating the vermis from the two lateral hemispheres. Middle panel: mutant cerebellum with lack of longitudinal fissures (arrowheads) and fusion of the two lateral hemispheres (the majority of cases). Lower panel: mutant cerebellum with separated hemispheres that are only rostrally connected (arrows). e Nissl-stained coronal sections of control and mutant cerebelli (3–4 weeks of age). Note the midline fusion of lateral hemisphere lobules in the mutants. v cerebellar vermis; asterisk (*) vermis-like midline structure. Scale bars in b, d, e: 1 mm. f Inversion of Smarcb1 exon 1 in genomic DNA from E14.5 mutant and control forebrain tissue detected by polymerase chain reaction (PCR). Three primer pairs are used in one reaction, leading to amplification of a 97-bp product in case of the wild-type allele (Smarcb1+), of a 200-bp product in case of the active, non-inverted, floxed allele (Smarcb1inv) due to loxP site and extra DNA sequences, and of a 361-bp product in case of the inactive inverted allele (Smarcb1inv Cre+). Gel electrophoresis of the PCR products shows the presence of inverted and non-inverted alleles in all mutant samples (m1–m5). g Smarcb1 transcript levels in E14.5 control (c2–c4) and mutant (m1–m5) forebrain tissue determined by quantitative reverse transcriptase-PCR. Primers binding to exons 1 and 2 and primers that specifically amplify one of the two Smarcb1 isoforms differing in exon 2 length were applied. Significantly reduced levels of all three cDNA PCR products were found in mutant (five animals) compared to control (three animals) samples. All bars display the mean with standard deviations. *p ≤ 0.05, **p ≤ 0.01 (unpaired two-tailed Student’s t test). Source data are provided as a Source Data file
