Increased apoptosis during neonatal brain development underlies the adult behavioral deficits seen in mice lacking a functional paternally expressed gene 3 (Peg3)

Inactivation of the maternally imprinted, paternally expressed gene 3 (Peg3) induces deficits in olfactory function, sexual and maternal behaviors, oxytocin neuron number, metabolic homeostasis and growth. Peg3 is expressed in a number of developing hypothalamic and basal forebrain structures and is a component of the P53 apoptosis pathway. Peg3 inactivation in neuronal cell culture lines inhibits P53 mediated apoptosis, which is important in the early postnatal development and sexual differentiation of the brain. In this study, we investigated the effect of inactivating the Peg3 gene on the incidence of caspase 3 positive cells (a marker of apoptosis) in 4‐ and 6‐day postpartum mouse brain. Inactivating the Peg3 gene resulted in an increase in the incidence of total forebrain caspase 3 positive cells at 4 and 6 days postpartum. Increases in specific neuroanatomical regions including the bed nucleus of the stria terminalis, nucleus accumbens, caudate putamen, medial pre‐optic area, arcuate nucleus, medial amygdala, anterior cortical and posteriodorsal amygdaloid nuclei, were also observed. In wild‐type mice, sex differences in the incidence of caspase 3 positive cells in the medial amygdala, bed nucleus of the stria terminalis, nucleus accumbens, arcuate nucleus and the M2 motor cortex, were also observed. This neural sex difference was ameliorated in the Peg‐3 mutant. These findings suggest that the neuronal and behavioral deficits seen in mice lacking a functional Peg3 gene are mediated by increases in the incidence of early neonatal apoptosis in neuroanatomical regions important for reproductive behavior, olfactory and pheromonal processing, thermoregulation and reward. © 2009 Wiley Periodicals, Inc. Develop Neurobiol, 2009     

Coadaptation in mother and infant regulated by a paternally expressed imprinted gene

This study investigates how a targeted mutation of a paternally expressed imprinted gene regulates multiple aspects of foetal and post-natal development including placental size, foetal growth, suckling and post-natal growth, weaning age and puberty onset. This same mutation in a mother impairs maternal reproductive success with reduced maternal care, reduced maternal food intake during pregnancy, and impaired milk let-down, which in turn reduces infant growth and delays weaning and onset of puberty. The significance of these coadaptive traits being synchronized in mother and offspring by the same paternally expressed imprinted gene ensures that offspring that have extracted 'good' maternal nurturing will themselves be both well provisioned and genetically predisposed towards 'good' mothering.     

A new cytotoxic lymphocyte-defined antigen coded by a gene closely linked to the H-3 locus

F1 complementation results indicate that a new gene, putatively controlling a minor histocompatibility antigen, is closely linked to the minor histocompatibility gene, H-3, in the fifth linkage group of chromosome 2 of the mouse. This gene controls a product that was capable of inducing as well as acting as a target for cytotoxic lymphocytes (CTL). The lytic activity of CTL developed in B10.LP-H-3D mice specific for the product of the new gene of B10 was restricted to target cells possessing H-2Db antigens. This contrasts to the H-2Kb-restricted activity of H-3.1 specific CTL.     

A new cytotoxic lymphocyte-defined antigen coded by a gene closely linked to theH-3 locus

F₁ complementation results indicate that a new gene, putatively controlling a minor histocompatibility antigen, is closely linked to the minor histocompatibility gene,H-3, in the fifth linkage group of chromosome 2 of the mouse. This gene controls a product that was capable of inducing as well as acting as a target for cytotoxic lymphocytes (CTL). The lytic activity of CTL developed in B10.LP-H-3^b mice specific for the product of the new gene of B10 was restricted to target cells possessing H-2D^b antigens. This contrasts to the H-2K^b-restricted activity of H-3.1 specific CTL.     

Detection and cloning of expressed sequences linked to a target gene

DNA markers tightly linked to a target gene are essential starting points for positional cloning. We combined ”differential display of mRNA” and ”bulked segregant analysis” in order to detect and clone ten expressed sequences as markers linked to a virus resistance gene in Phaseolus vulgaris. The combination of these two procedures could be used in lieu of positional cloning, provided polymorphisms detectable by differential display exist in the target gene. Isolation of expressed sequences from specific chromosome regions can also be accomplished by combining these procedures. Received: 8 July 1999 / Accepted: 21 March 2000     

水稻长穗颈基因eui紧密连锁SSR标记获得

02428h是从半矮秆材料02428体细胞培养后代中发现的隐性高秆突变体, 其株高性状由1对长穗颈基因eui和1对半矮秆基因sd-1共同控制。以02428h与半矮秆材料南京11杂交的F₂为作图群体, 利用Gramene公布的SSR标记和根据NCBI中的BAC序列自己新开发的SSR标记, 将eui基因定位在第5染色体上的RM3673和RM0012之间, 两侧遗传距离分别为0.3 cM和1.0 cM, 为该基因的分子标记辅助选择奠定了基础。     

The angiotensinogen gene of Swiss mice is closely linked to a retrovirus-like element

Angiotensinogen is cleaved by renin and angiotensin-converting enzyme to liberate the potent vasocontrictor peptide angiotensin II. We have recently identified a cis-acting genetic lesion associated with high levels of angiotensinogen mRNA in the testis and salivary gland of Swiss mice. To determine the molecular basis of this mutation, the Swiss angiotensinogen gene was cloned, and its structure was compared to that from a low-expressing strain (BALB/c). I show that a retrovirus-like element belonging to the intracisternal A-particle gene family has been inserted 9 kb upstream from the cap site of the Swiss angiotensinogen gene. This intracisternal A-particle, named IAP-Agt, segregated concordantly with angiotensinogen expression phenotypes in CXB recombinant inbred mice. However, genomic Southern analysis showed that IAP-Agt was present in some, but not all, inbred laboratory mouse strains displaying high levels of angiotensinogen gene expression. On the basis of this evolutionary evidence, it is unlikely that IAP-Agt is the cause of the angiotensinogen mutation. It is intriguing that Ren-2, the duplicated mouse renin gene, is expressed to high levels in the male salivary gland and also contains a transposed intracisternal A-particle genome.     

A new genetic model proposing that the Se gene is a structural gene closely linked to the H gene.

The Se gene is classically considered as a regulatory gene controlling the expression of the structural gene H in external secretions. Under this hypothesis, Bombay (h/h) individuals should not be able to express the Se gene. Statistical analysis of the 44 published Bombay pedigrees suggests on the contrary that there is no suppression of Se in Bombay individuals, and that both Se and H loci can be fully expressed at the phenotypic level. Based on a lod score of 12.9 at 1% recombination units and the existence of two different acceptors for the biosynthesis of the H antigen, a new genetic model is proposed in which H and Se would be two closely linked structural genes coding for two different 2-alpha-L-fucosyltransferases.     

Evolution of closely linked gene pairs in vertebrate genomes

The orientation of closely linked genes in mammalian genomes is not random: there are more head-to-head (h2h) gene pairs than expected. To understand the origin of this enrichment in h2h gene pairs, we have analyzed the phylogenetic distribution of gene pairs separated by less than 600 bp of intergenic DNA (gene duos). We show here that a lack of head-to-tail (h2t) gene duos is an even more distinctive characteristic of mammalian genomes, with the platypus genome as the only exception. In nonmammalian vertebrate and in nonvertebrate genomes, the frequency of h2h, h2t, and tail-to-tail (t2t) gene duos is close to random. In tetrapod genomes, the h2t and t2t gene duos are more likely to be part of a larger gene cluster of closely spaced genes than h2h gene duos; in fish and urochordate genomes, the reverse is seen. In human and mouse tissues, the expression profiles of gene duos were skewed toward positive coexpression, irrespective of orientation. The organization of orthologs of both members of about 40% of the human gene duos could be traced in other species, enabling a prediction of the organization at the branch points of gnathostomes, tetrapods, amniotes, and euarchontoglires. The accumulation of h2h gene duos started in tetrapods, whereas that of h2t and t2t gene duos only started in amniotes. The apparent lack of evolutionary conservation of h2t and t2t gene duos relative to that of h2h gene duos is thus a result of their relatively late origin in the lineage leading to mammals; we show that once they are formed h2t and t2t gene duos are as stable as h2h gene duos.     

Identification and developmental expression analysis of a novel homeobox gene closely linked to the mouse Twirler mutation

The Twirler mutation arose spontaneously and causes inner ear defects in heterozygous and cleft lip and/or cleft palate in homozygous mutant mice, providing a unique animal model for investigating the molecular mechanisms of inner ear and craniofacial development. Here, we report the identification of a novel homeobox gene, Iroquois-related homeobox like-1 (Irxl1), from the Twirler locus. Irxl1 encodes a TALE-family homeodomain protein with its homeodomain exhibiting the highest amino acid sequence identity (54%) to those of invertebrate Iroquois and vertebrate Irx subfamily members. The putative Irxl1 protein lacks the Iro-box, a conserved motif in all known members of the Irx subfamily. Searching the databases showed that Irxl1 orthologs exist in Xenopus, chick, and mammals. In situ hybridization analyses of mouse embryos at various developmental stages showed that Irxl1 mRNA is highly expressed in the frontonasal process and palatal mesenchyme during primary and secondary palate development. In addition, Irxl1 mRNA is strongly expressed in mesenchyme surrounding the developing inner ear, in discrete regions of the developing mandible, in the dermamyotome during somite differentiation, and in a subset of muscular structures in late embryonic stages. The developmental expression pattern indicates that Irxl1 is a good candidate gene for the Twirler gene.     

Two copies of the human apolipoprotein C-I gene are linked closely to the apolipoprotein E gene

The gene for human apolipoprotein (apo) C-I was selected from human genomic cosmid and lambda libraries. Restriction endonuclease analysis showed that the gene for apoC-I is located 5.5 kilobases downstream of the gene for apoE. A copy of the apoC-I gene, apoC-I', is located 7.5 kilobases downstream of the apoC-I gene. Both genes contain four exons and three introns; the apoC-I gene is 4653 base pairs long, the apoC-I' gene 4387 base pairs. In each gene, the first intron is located 20 nucleotides upstream from the translation start signal; the second intron, within the codon of Gly-7 of the signal peptide region; and the third intron, within the codon for Arg39 of the mature plasma protein coding region. The upstream apoC-I gene encodes the known apoC-I plasma protein and differs from the downstream apoC-I' gene in about 9% of the exon nucleotide positions. The most important difference between the exons results in a change in the codon for Gln-2 of the signal peptide region, which introduces a translation stop signal in the downstream gene. Major sequence differences are found in the second and third introns of the apoC-I and apoC-I' genes, which contain 9 and 7.5 copies, respectively, of Alu family sequences. The apoC-I gene is expressed primarily in the liver, and it is activated when monocytes differentiate into macrophages. In contrast, no mRNA product of the apoC-I' gene can be detected in any tissue, suggesting that it may be a pseudogene. The similar structures and the proximity of the apoE and apoC-I genes suggest that they are derived from a common ancestor. Furthermore, they may be considered to be constituents of a family of seven apolipoprotein genes (apoE, -C-I, -C-II, -C-III, -A-I, -A-II, and -A-IV) that have a common evolutionary origin.