Fig. 1. Double knockout (Abr-/-;Bcr-/-) mice display abnormal cerebellar development. (A) Schematic drawing of the wild-type Abr locus, the targeting vector and the mutant allele. The targeting vector was constructed by inserting a PGK-neo-pA cassette into the NcoI site of exon 3. The hatched box represents the XhoI-HindIII fragment which was used as an external 3' probe. The predicted sizes of HindIII fragments hybridizing to this probe are shown above the wild-type locus and below the targeted locus. Restriction enzymes: H, HindIII; Bg, BglII; N, NcoI; B, BamHI; Xh, XhoI. (B-E) Hematoxylin and Eosin stained midsagittal sections through wild-type (B,D) and double null mutant cerebellum (C,E). Samples were taken at 11 days (B,C; insets at postnatal day 0) and 3 months (D-I) of age. Note abnormal foliation (E, asterisk) and the presence of persistent granule cells on the surface of the molecular layer (E, arrow). (F-I) The double knockout specimens display fusion of folia (F, arrow), abnormal foliation (G) in the anterior folia (III and IV) of the cerebellum, and presence of abnormal ectopic granule cells (G-H, arrows) when compared with age-matched wild-type controls. There was a rosette-like arrangement of the ectopic granule cells around an eosinophilic fibrillary core (I, arrow). Vermal folia are indicated with roman numerals, III-X. Anterior is towards the left of each photograph. Ce, cerebellum; IC, inferior colliculus. Scale bars: 1 mm in B-E; 300 µm in insets of B,C; 100 µm in D-H; 50 µm in I.
