Expression of the dystrophin‐related protein (utrophin) gene during mouse embryogenesis

Abstract

The utrophin (UTRN) locus is the autosomal homologue of the DMD (Duchenne muscular dystrophy) gene and encodes a protein, utrophin which is thought to be upregulated in the absence of dystrophin. In this study the spatial and temporal expression of the UTRN gene has been examined during mouse embryogenesis and compared with that of the DMD gene. The patterns of expression of these two genes are very different. Whilst DMD is expressed largely in mesodermal derivatives such as cardiac and striated muscle, UTRN shows a more widespread distribution and is expressed in neurat tube, tissues which originate from neural crest and a variety of other sites of non-neural origin. In early embryos UTRN transcripts initially accumulate in the mid-neural plate and thereafter in the caudal neural tube. UTRN mRNA then becomes abundant in a subset of neural crest cell derived tissues, in particular the spinal and facial ganglia and ossifying facial cartilages. UTRN is also expressed in a variety of other sites and organs such as the tendon primordia in the digits, the pituitary, thyroid and adrenal glands, cardiac muscle, kidney and lung, follicles of the vibrissae and the outflow tract of the heart. Several patterns of UTRN expression are apparent and we discuss the possibility that these can be ascribed to a family of mRNAs transcribed from the UTRN gene using alternative promoters. 0 1993 Wiley-Liss, Inc.

Dystroglycan mRNA expression during normal and mdx mouse embryogenesis: A comparison with utrophin and the apo‐dystrophins

“…It is particularly noticeable that there is no apparent evidence of upregulation of either utrophin or apo-dystrophin mRNA expression in the heart and myotomes of the rndx embryo. These are both sites in which dystro- phin would normally be present at moderate levels at this stage of development (Houzelstein et al, 1992;Schofield et al, 1993). The pattern of utrophin expression is the same in mdx and normal embryos with transcripts confined to the caudal neural tube (Fig.…”

“…2D,E) and tendon primordia of the digits (compare Fig. 1E and 4D, and see also Schofield et al, 1993). One site where the patterns of expression of utrophin and dystroglycan clearly coincide is in the ependymal cells lining the central canal of the developing spinal cord; this is also a site where the short dystrophin transcript, Dp71, is relatively abundant.…”

“…The utrophin probe consisted of a 1.3 kb EcoRI-Hind111 fragment from the 3'UTR of utrophin (Schofield et al, 1993) and the Dp71 (apodystrophin-1) probe, 107 bp, which contains 55 bp specific to the Dp71 transcript. This probe has been described previously and has been shown to detect only Dp71 transcripts (Schofield et al, 1994).…”

UTRN on chromosome 6q24 is mutated in multiple tumors

“…UTRN mutation in multiple tumors Y Li et al UTRN shares similarity with DMD at both the nucleic acid (65%) level and the amino-acid level (80%). DMD is most abundant in skeletal and cardiac muscle, whereas UTRN is expressed ubiquitously (Schofield et al, 1993). The introns of both genes contain a high percentage of repeat sequences, with 28.4% for UTRN and 32.1% for DMD (Pozzoli et al, 2002).…”

Muscular dystrophy begins early in embryonic development deriving from stem cell loss and disrupted skeletal muscle formation

“…Myf5 marks the embryonic myoblast population; it is expressed in myotome (E8.5) before myotube differentiation is initiated and is found in all muscle groups throughout myogenesis (Hadchouel et al, 2003;Ott et al, 1991). Dystrophin is expressed at a crucial stage in myotome differentiation (E9.5), one day later than Myf5 expression at E8.5, and 24 hours before the appearance of the first fully differentiated myotomal (epaxial) myotubes and the first expression of myosin heavy chain (MyHC) (E10.5) (Houzelstein et al, 1992;Ott et al, 1991;Schofield et al, 1993). Early hypaxial and secondary myogenesis are severely disrupted and delayed in mdx embryos, as shown by the late appearance of the FMyHC, Pax7 and caveolin-3 proteins and by the incomplete formation and disorganisation of mdx musculature at between E11.5 and E13.5 (Figs 1, 6; supplementary material Fig.…”