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About 12-17% of the embryos obtained by mating mice carrying the In(X)1H or Paf mutations are of the 39,X (X0) genotype. Depending on the mutant mice used for mating, the monosomic X chromosome can be inherited from the paternal ([X.sup.P]) or the maternal ([X.sup.M]) parent. The [X.sub.P]0 embryos display developmental retardation at gastrulation and early organogenesis. [X.sup.P]0 embryos also display poor development of the ectoplacental cone, which is significantly smaller in size and contains fewer trophoblasts than XX siblings. In contrast, [X.sup.M]0 embryos develop normally and are indistinguishable from XX littermates. In both types of X0 embryos, an X-linked lacZ transgene is expressed in nearly all cells in both the embryonic and the extraembryonic tissues, suggesting that X inactivation does not occur when only one X is present. Of particular significance is the maintenance of an active [X.sup.P] chromosome in the extraembryonic tissues where normally the paternal X chromosome is preferentially inactivated in XX embryos. The differential impact of the inheritance of X chromosomes from different parents on the development of the X0 embryos raises the possibility that the [X.sup.P] is less capable than the [X.sup.M] in providing the appropriate dosage of X-linked activity that is necessary to support normal development of the embryo and the ectoplacental cone. Alternatively, the development of the [X.sup.P]0 embryo may be compromised by the lack of activity of one or several X-linked genes which are expressed only from the maternal X chromosome. Without the activity of these genes, embryonic development may be curtailed even though all other loci on the [X.sup.P] chromosome are actively transcribed.

The requirement of Y-chromosome activity for the differentiation of somatic cells and germ cells was studied in the fetal gonads of X/[XSxr.sup.a] mouse embryos where the activity of the [Sxr.sup.a] fragment of the Y chromosome is influenced by the inactivation and reactivation of the X chromosome. In the interstitial somatic cells, random inactivation of the X and the [XSxr.sup.a] chromosomes took place which was revealed by the mosaic expression of an X-linked lacZ transgene. The Sertoli cells, however, displayed a preferentially active [XSxr.sup.a] chromosome and the presence of [Sxr.sup.a]-active Sertoli cells was associated with the morphogenesis of testicular tubules in the sex-reversed gonads. The activity of the Y-chromosome fragment is therefore necessary for the differentiation of the Sertoli cells which may direct the development of the testis. The expression pattern of the X-linked transgene in X/[XSxr.sup.a] germ cells suggests that both the X and the [XSxr.sup.a] chromosomes are active. This finding suggests that the presence of [Sxr.sup.a] has no impact on the reactivation of the X chromosome in the germ cells and that the X chromosome can be reactivated even though the germ cells are found in the testicular environment. Our results are consistent with the concept that the activity of genes on the [XSxr.sup.a] fragment is essential for the differentiation of Sertoli cells and the morphogenesis of the testis, but not for premeiotic differentiation of germ cells in sex-reversed mice.

An unusual mutation affecting nucleotide 14482 of the mitochondrial ND6 gene has been found in a Turkish matrilineal pedigree associated with bilateral optic atrophy. The optic neuropathy is consistent with Leber hereditary optic neuropathy (LHON), but the three previously identified LHON mutations were not found. There is strong evidence that the 14482 mutation can be considered the primary etiological source of the optic neuropathy in this family.

X‐linked retinitis pigmentosa (XLRP) accounts for a significant proportion of certifiable blindness in working‐age adults. The objectives of this study were to: (1) synthesize the best available evidence regarding the natural history of disease progression and (2) identify the best current clinical biomarkers for monitoring disease progression, which will be important in planned gene therapy trials for this condition. Patient population: XLRP affected males. Main outcomes: A systematic review of the literature was undertaken with data sought on overall annual progression for clinical biomarkers using optical coherence tomography (OCT), fundus autofluorescence (FAF), visual acuity, electroretinography and visual fields. To assess which outcome was best for monitoring progression, data on reliability, interocular correlation and structure‐function correlation were extracted. A total of 17 studies met the inclusion criteria. Studies estimated progression at between 4% to 19% per year with longitudinal data. Where an overall model was produced with cross‐sectional data, the trend was usually best fit by a logarithmic function with an annual exponential decline rate between 4.7% and 8.0%. The evidence suggested the ellipsoid zone (EZ) width on OCT and outer ring area (ORA) on FAF as the most useful biomarkers having excellent interocular symmetry, reproducibility and functional correlation. Using different clinical biomarkers, XLRP progresses at a rate of 4 to 19% per year. Ellipsoid zone (EZ) width and ORA are the most robust biomarkers with the potential to be used in trials where one eye serves as a control for the other. [ABSTRACT FROM AUTHOR]