Karyotype and idiogram of chromosome 7 from p^100H showing the presence of paracentric inversion with breakpoints in bands 7B5 and 7F1. The central chromosome is a composite made by cutting and inverting the appropriate segment from the normal chromosome 7 (N7). The banding pattern of this composite chromosome then resembles that from a p^100H/+ heterozygote (p^100H).

(A) Mouse multiple tissue Northern blot. Each lane contains 2 μg of poly(A)⁺ RNA from the tissues indicated hybridized with ³²P-labeled 575 bp Sox6 cDNA fragment (nucleotides 1353–1927). Control hybridization with β-actin was performed to confirm equal loading of RNAs (data not shown). sk, skeletal. (B) Mouse embryonic multiple tissue Northern blot hybridized with the same probe as A. Each lane contains 2 μg of poly(A)⁺ RNA isolated from embryos whose ages are listed above each lane as embryonic day (ED). Numbers on left are sizes of standard marker fragments.

(A) A schematic diagram of the p locus and the Sox6 locus on mouse chromosome 7. WT, wild type; p^100H, p^100H mutant. Primers used for RT-PCR are listed underneath each exon (23, 24, x, y, z). Nucleotide sequences of the primers are described in Materials and Methods. 5′R-1–15 is the first chimeric cDNA clone isolated and was used to identify the inversion breakpoints in the p^100H mutation (see text). (B) RT-PCR products amplified from wild-type (+) and the p^100H homozygote (p^100H) brain cDNA using primers listed. +RT and −RT represent synthesis with or without RT, respectively in a cDNA reaction. Sizes of the marker standard fragments (M: pBR322 MspI digest; New England Biolabs) are from the top: 622 bp, 527 bp, 404 bp, 307 bp, 238/242 bp, 217 bp. The expected sizes of the RT-PCR products are: 292 bp for p, 575 bp for Sox6, 224 bp for 5′p-3′Sox6, and 643 bp for 5′Sox6-3′p. The two fragments seen in p^100H (+RT) lane of p were cloned and sequenced. Both fragments (327 bp and 480 bp) have no significant sequence matches with the p gene except for the primer sequences and are therefore artifactual. (C) Amino acid sequence in the vicinity of the breakpoints. The predicted amino acid sequences of the chimeric transcripts are shown below the nucleotide sequence. Arrowhead indicates the breakpoint, and the numbers above and below it correspond to nucleotide numbers of the breakpoint in the p gene cDNA (GenBank accession no. M97900) or the Sox6 gene cDNA (GenBank accession no. U32614).

Electron micrographs of skeletal and cardiac muscle cells (A–D) and ECG of wild-type (E) and the mutant (F). WT, the wild-type littermate (A and C), p^100H, the p^100H homozygote (B and D). N, nucleus. Arrow heads in B and D indicate deposits found in the mutant muscle cells. The scale bar in D is equal to 4 μm. Representative ECG of the wild type (E) and the mutant (F) are shown. The small arrow indicates P-wave, activation of the atria, and the large arrow indicates QRS-complex, activation of the ventricles. The ECG of F shows the third degree (complete) heart block observed in a postnatal day-12 p^100H mouse less than 24 h before death.