The myc family of cellular oncogenes contains three known members. The N-myc and c-myc genes have 5'-noncoding exons, strikingly homologous coding regions, and display similar oncogenic potential in an in vitro transformation assay. The L-myc gene is less well characterized, but shows homology to N-myc and c-myc (ref. 6; also see below). c-myc is expressed in most dividing cells, and deregulated expression of this gene has been implicated in the development of many classes of tumours. In contrast, expression of N-myc has been found only in a restricted set of tumours, most of which show neural characteristics; these include human neuroblastoma, retinoblastoma and small cell lung carcinoma (SCLC). L-myc expression has so far been found only in SCLC. Activated N-myc and L-myc expression has been implicated in oncogenesis; for example, although N-myc expression has been found in all neuroblastomas tested, activated (greatly increased) N-myc expression, resulting from gene amplification, is correlated with progression of the tumour. We now report that high-level expression of N- and L-myc is very restricted with respect to tissue and stage in the developing mouse, while that of c-myc is more generalized. Furthermore, we demonstrate that N-myc is not simply a neuroectoderm-specific gene; both N- and L-myc seem to be involved in the early stages of multiple differentiation pathways. Our findings suggest that differential myc gene expression has a role in mammalian development and that the normal expression patterns of these genes generally predict the types of tumours in which they are expressed or activated.

N-myc, a cellular gene related to the c-myc proto-oncogene, was originally identified on the basis of its very frequent amplification and overexpression in a restricted set of tumours, most notably human neuroblastomas. That N-myc may have a causal role in the genesis of these tumours is suggested by the observation that in the rat embryo fibroblast co-transformation assay it has a transforming potential similar to that of c-myc. The apparent structural and functional homology of N-myc and c-myc suggests that they may be members of the same protooncogene family. However, despite these apparent similarities, expression of the two genes appears to be dramatically different with respect to tumour specificity, as well as tissue and developmental stage specificity. To further elucidate the common and unique aspects of N-myc and c-myc gene structure and function in normal and transformed cells, we have determined the organization of human N-myc and the nucleotide sequence of its messenger product, and we report here that N-myc and c-myc have a similar intron/exon structure and that their protein products share regions of significant homology.

To investigate the role of intronic immunoglobulin heavy chain (IgH) enhancer (E mu) in generating accessibility of the JH locus for VDJ recombination, we generated ES cells in which E mu or its flanking sequences were mutated by replacement with or insertion of an expressed neor gene. Heterozygous mutant ES cells were used to generate chimeric mice from which pre‐B cell lines were derived by transformation of bone marrow cells with Abelson murine leukemia virus (A‐MuLV). Comparison of the rearrangement status of the normal and mutated alleles in individual pre‐B cell lines allowed us to assay for cis‐acting effects of the mutations. Replacement of a 700 bp region immediately downstream from the core E mu [which includes part of the 3′ matrix associated region (MAR) and the I mu exon] had no obvious effect on rearrangement of the targeted allele, indicating that insertion of a transcribed neor gene into the JH‐C mu intron does not affect JH accessibility. In contrast, replacement of an overlapping 1 kb DNA fragment that contains the E mu resulted in a dramatic cis‐acting inhibition of rearrangement, demethylation and germline transcription of the associated JH locus. Surprisingly, insertion of the neor gene into the 5′ MAR sequence approximately 100 bp upstream of the core E mu also dramatically decreased recombination of the linked JH locus; but, in many lines, did not prevent demethylation of this locus. We conclude that integrity of the E mu and upstream flanking sequences is required for efficient rearrangement of the JH locus and that demethylation of this locus, per se, does not necessarily make it a good substrate for VDJ recombination.

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Cesarean delivery is a commonly performed operation and accounts for nearly one-third of all births in the United States. Although it is a safe procedure, cesarean delivery has a variety of acute and chronic complications that prompt imaging with ultrasonography (US), computed tomography, and magnetic resonance imaging. Acute complications include hematomas in specific locations that are unique to the procedure, as well as a variety of infections. A bladder flap hematoma occurs in the space between the bladder and the lower uterine segment, whereas a subfascial hematoma is an extraperitoneal collection located in the prevesical space posterior to the rectus muscles and anterior to the peritoneum. Puerperal infections after cesarean delivery include abscesses, wound infections and dehiscence, uterine dehiscence and rupture, and pelvic thrombophlebitis. The prevalence of chronic complications related to the healed cesarean delivery scar is unknown, but the scar may result in technical limitations for pelvic US due to the adhesions between the anterior lower uterine segment and the anterior abdominal wall. The cesarean delivery scar also leaves the patient susceptible to several unique diagnoses. A cesarean scar "niche" is a tethering of the endometrium that can serve as a reservoir for intermenstrual blood and fluid. Intrauterine devices can be malpositioned in the cesarean delivery scar, and endometrial implants can develop in the abdominal wall years after surgery. These patients are also at increased risk for implantation abnormalities including cesarean scar ectopic pregnancy, retained products of conception, and placenta accreta. Familiarity with the normal postoperative findings following cesarean delivery is necessary to recognize acute and chronic complications, which are being encountered with increasing frequency.