Neurotensin is a tridecapeptide that plays several neurotransmitter or neuromodulatory roles both in the central nervous system and in the periphery. These actions are mediated by a high-affinity receptor (Ntsr). Both rat and human cDNAs encoding high-affinity receptors have been recently cloned. The availability of Ntsr probes allowed us to localize the corresponding genes on the mouse and human chromosomes. The present data demonstrate that the Ntsr gene is assigned to the H region of the mouse Chromosome (Chr) 2 and to the long arm of the human Chr 20.

Animals↗

PubMed1994

Clinical and molecular study of DiGeorge sequence.

DiGeorge sequence (DGS) is a developmental field defect of the third and fourth pharyngeal pouches. The cardinal features of the syndrome are hypo- or aplasia of the thymus and parathyroids, congenital heart defect of the conotruncal type and characteristic facial dysmorphism. Such a pattern of malformations has been associated with various conditions but it is now well established that most cases of DGS are due to haplo-insufficiency of the chromosome 22q11 region. We report here a series of 16 patients, including a familial case. Minimal criteria for inclusion in this series were two or more of the following features: conotruncal heart defect, hypocalcaemia, hypoplastic/absent thymus and typical facial dysmorphism. Molecular analysis with specific probes of the 22q11 region was conducted in all patients according to two methods, fluorescent in situ hybridization and DNA dosage analysis. A deletion was found at the molecular level in all patients. We emphasize the fact that clinical analysis remains an important step of the diagnosis. The implication of these molecular techniques on diagnosis, prognosis and genetic counselling of DGS are discussed.

Child, Preschool↗

PubMed1994

Chromosomal mapping of human adenylyl cyclase genes type III, type V and type VI.

Adenylyl cyclase activity plays a central role in the regulation of most cellular processes. At least eight different adenylyl cyclases have been identified, which are endowed with various and sometimes opposing regulatory properties. Recently we have localized the human genes encoding two of these adenylyl cyclases: the gene for type II adenylyl cyclase is located on chromosome 2 (sub-band 2p15.3), the gene for type VIII is located on chromosome 8 (sub-band 8q24.2). More recently the type I gene has been located on chromosome 7 (sub-band 7p12-7p13). Using in situ hybridization, we have now localized the genes for three other adenylyl cyclases: the type III gene has been localized on chromosome 2 in the sub-band 2p22-2p24, the type V gene on chromosome 3 at position 3q13.2-3q21, and the type VI gene on chromosome 12 at position 12q12-12q13. It therefore appears that all adenylyl cyclase genes, known at present are located on different chromosomes and thus are likely to be independently regulated.

Adenylyl Cyclases↗

PubMed1994

The mouse homeoprotein mLIM-3 is expressed early in cells derived from the neuroepithelium and persists in adult pituitary.

LIM-homeodomain proteins are important in cell lineage specification and possibly mediate transcriptional processes in eukaryotes. During the screening of a mouse pituitary cDNA library, we isolated a partial cDNA coding for a novel gene product that exhibited a predicted amino-terminal sequence similar to the homeobox of LIM-homeodomain-containing proteins. Reverse transcriptase-polymerase chain reactions (RT-PCR) performed on mouse pituitary mRNA using degenerate oligonucleotides based on the conserved LIM-domain sequences, allowed the extension of the 5' end of the sequence. The composite 2.2-kb cDNA structure predicts a 400-amino-acid-long novel mouse (m) protein, called mLIM-3. This name was chosen since within the 59-amino-acid homeodomain, it exhibits 97% sequence identity to a recently reported Xenopus homologue xLIM-3. The gene coding for mLIM-3 maps to the murine chromosome 2, most probably within the 2B band. Based on sequence characteristics, we suggest that LIM-3 belongs to a distinct subfamily of LIM-containing homeoproteins. Ontogeny studies using in situ hybridization demonstrated that mLIM-3 transcripts can be detected on embryonic day 11 (e11) in the primordium of the hypophysis. Following a maximum between e12 and e14, lower levels persisted into adulthood, where mLIM-3 was expressed primarily in the anterior and intermediate lobes of the pituitary. These results were confirmed by Northern blot analysis in adult mice which revealed a 2.4-kb pituitary mRNA transcript. mLIM-3 transcripts were also detected in pituitary cell lines such as the somatotrophs GH3 and GH4C1, the gonadotroph alpha T3-1, and the corticotroph AtT-20 cells, but not in 20 other cell lines derived from peripheral, endocrine, and neural tissues. Starting from e11, we also observed a transient expression of mLIM-3 in the ventral part of the spinal cord, pons, and medulla oblongata, reaching a maximum at e13 and from p7 onward, the expression of this transcript is no longer detectable. mLIM-3 is also expressed in the pineal gland with high levels observed at e20. These data suggest a potential role for mLIM-3 in the transcriptional regulation of certain genes during morphogenesis and/or maintenance of the differentiated state of the pituitary, motor neurons, and pineal gland.

Amino Acid Sequence↗

PubMed1994

A novel X gene with a widely transcribed Y-linked homologue escapes X-inactivation in mouse and human.

A new gene, designated Smcx, was cloned from the mouse X chromosome by its homology to the Y located gene Smcy. Using direct in situ hybridisation Smcx was mapped to the distal end of the mouse X chromosome (XF2-XF4) and its human homologue, SMCX, was mapped to proximal Xp (Xp11.1-Xp11.2). Further meiotic mapping in the mouse placed Smcx in the Plp-Pdha1 interval. As Smcx/SMCX have widely expressed homologues on the Y chromosome, they appeared good candidates for genes that escape X-inactivation. In the human we show this to be the case as SMCX is expressed in hamster-human hybrids containing either an active or inactive human X chromosome. Two alleles of Smcx were found to be expressed in T(16;X)16H female mice despite the intact X chromosome being inactive in all cells. This indicates that Smcx is also not subject to X-inactivation and provides the first example of a gene that is expressed from inactive and active X chromosomes in the mouse.

Alleles↗

PubMed1994

Chromosomal localization of two genes encoding human ras exchange factors: SOS1 maps to the 2p22-->p16 region and SOS2 to the 14q21-->q22 region of the human genome.

The human SOS1 and SOS2 genes encode proteins that control GDP-->GTP exchange on ras proteins and are involved in signal transduction by tyrosine kinase receptors. In situ hybridization shows that SOS1 maps to 2p22-->p16 and SOS2 to 14q21-->q22 in the human genome.

Chromosome Banding↗

PubMed1994

Isolation and characterization of human cDNAs and genomic DNAs encoding alpha-4(IV) and alpha-6(IV) chains reveal the presence of a distinct subclass of collagen IV genes.

Explore the source record for details and available documents.

Amino Acid Sequence↗

PubMed1994

Programmed cell death is affected in the novel mouse mutant Fused toes (Ft).

We have identified a novel dominant mouse mutant that is characterised by fused toes on the fore limbs and a thymic hyperplasia, in heterozygous animals. Homozygosity of the mutation leads to malformation of the developing brain, lost of the genetic control of left-right asymmetry and to death around day 10 of development. Analysis of both limb development and induction of apoptosis in immature thymocytes in vitro suggest that programmed cell death is affected by the mutation. Since the mutation was caused via a transgene insertion we were able to map it to the D region on mouse chromosome 8. So far, no mutation that affects programmed cell death has been mapped to this chromosome. Thus, this mutation will allow the identification of a novel gene involved in programmed cell death during mammalian development.

Animals↗

PubMed1994

Molecular characterization and chromosome localization of a human angiotensin II AT2 receptor gene highly expressed in fetal tissues.

The gene encoding the human angiotensin II (AT2) receptor exists as a single copy and contains no intron in its coding region. Its nucleotide sequence is identical to that of cDNA clones isolated from human myometrial library. In addition, binding properties of the corresponding receptor expressed in COS cells are identical to those of endogenous AT2 receptors from human myometrium. The human AT2 receptor gene translates into a polypeptide of 363 amino-acid residues that belongs to the seven transmembrane domains receptor superfamily. This polypeptide shows 92% amino-acid sequence homology and the same pharmacological profile as AT2 receptors recently isolated from rat and mouse. The AT2 receptor gene maps to the X chromosome in man (region Xq24-q25) as well as in mouse (region XA2-A4). These findings open new perspectives regarding a potential involvement of AT2 receptors in X-linked congenital diseases. Expression of AT2 receptor mRNA is found in human myometrium, fallopian tubes and adrenals, and at extremely high levels in fetal kidney and intestine. These results indicate that AT2 receptor gene expression is regulated during human embryonic development, and support the hypothesis that AT2 receptors may play a role in organogenesis.

Amino Acid Sequence↗

PubMed1994

[Angelman syndrome].

The Angelman syndrome is a neurological disorder characterized by constant features: severe mental retardation, easily provoked laughter, ataxia, absent speech, seizures. Most cases are sporadic but familial cases have been reported. About 60 to 70% of cases are due to an interstitial deletion on the maternally inherited chromosome 15 in the region q11-q13. Rare cases result from paternal disomy. In 30% of patients, neither maternal by inherited deletion, nor paternal disomy, can be found. In this category of patients recurrence risk for sibs is high and molecular mechanisms are not completely known. They appear to be more complex than previously suggested. It is clear that this syndrome is a genetically heterogeneous group. The main example of genomic imprinting in human pathology, Angelman syndrome is now a model in research for understanding molecular mechanisms underlying imprinting.

Angelman Syndrome↗

PubMed1994

Cloning and characterization of human type 2 and type 3 inositol 1,4,5-trisphosphate receptors.

We have cloned cDNAs coding for human type 2 and type 3 and part of type 1 inositol 1,4,5-trisphosphate receptors (IP3Rs). The complete nucleotide sequences for type 2 and type 3 receptors were determined and the pharmacological properties of the latter were characterized. Human type 2 and type 3 IP3Rs are 2701 amino acids and 2671 amino acids long, respectively, and have significant sequence homologies as well as structural similarities including the six membrane-spanning regions near the C-termini when compared with the rat or mouse counterpart. COS-7 cells transfected with human type 3 IP3R showed characteristic inositol 1,4,5-trisphosphate (IP3)-binding properties with Kd values of 28.8 nM. The order of potency of competition with IP3 was Ins(1,4,5)P3 (IP3) > Ins(2,4,5)P3 > Ins(1,3,4,5)P4 > Ins(1,2,3,4,5,6)P6. Type 2 and type 3 IP3Rs were mapped to human chromosomes 12p11 and 6p21, respectively, by in situ hybridization. cDNA cloning of the human IP3Rs allowed us to identify the types of the receptor expressed in various human hematopoietic and lymphoma cell lines. The type 3 receptor was present in all of cell lines tested, while the type 1 or 2 receptor was expressed in only particular cell types. The differential expression of the IP3R types could confer the cell-specific regulation on the IP3/Ca2+ signalling.

Amino Acid Sequence↗

PubMed1993

Myelin/oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex.

Myelin/oligodendrocyte glycoprotein (MOG) is found on the surface of myelinating oligodendrocytes and external lamellae of myelin sheaths in the central nervous system, and it is a target antigen in experimental autoimmune encephalomyelitis and multiple sclerosis. We have isolated bovine, mouse, and rat MOG cDNA clones and shown that the developmental pattern of MOG expression in the rat central nervous system coincides with the late stages of myelination. The amino-terminal, extracellular domain of MOG has characteristics of an immunoglobulin variable domain and is 46% and 41% identical with the amino terminus of bovine butyrophilin (expressed in the lactating mammary gland) and B-G antigens of the chicken major histocompatibility complex (MHC), respectively; these proteins thus form a subset of the immunoglobulin superfamily. The homology between MOG and B-G extends beyond their structure and genetic mapping to their ability to induce strong antibody responses and has implications for the role of MOG in pathological, autoimmune conditions. We colocalized the MOG and BT genes to the human MHC on chromosome 6p21.3-p22. The mouse MOG gene was mapped to the homologous band C of chromosome 17, within the M region of the mouse MHC.

Aging↗

PubMed1993

Identification of a new interferon-alpha-inducible gene (p27) on human chromosome 14q32 and its expression in breast carcinoma.

A new complementary DNA, p27, has been cloned and sequenced from estradiol-treated MCF7 human breast carcinoma cells. It encodes a putative highly hydrophobic protein of 122 amino acids which has a 33% overall sequence similarity to the product of the 6-16 gene (R. L. Friedman, S. P. Manly, M. McMahon, I. M. Kerr, and G. R. Stark, Cell, 38: 745-755, 1984), which is transcriptionally induced by interferons of the alpha/beta type. We demonstrate here that the p27 gene, which is located in band q32 of human chromosome 14, is also induced by interferon-alpha in human cell lines of different origin and that expression is independent of the presence of estradiol receptor in the cells. High levels of p27 RNA were found in vivo in approximately 50% of primary human breast carcinomas (21 were tested by Northern blotting). In situ hybridization to some of the p27-overexpressing tumors showed that the p27 RNA is localized in cancer cells and sometimes also in fibroblastic cells of tumor stroma. p27 RNA levels in the tumors did not correlate with the presence of estrogen receptor or with the expression of the estrogen-induced pS2 gene. Further studies are now necessary to elucidate the cause of p27 gene overexpression in breast carcinoma and in particular to determine whether it corresponds to chromosomal rearrangements in the 14q32 region and/or to induction by interferons of the alpha/beta type.

Amino Acid Sequence↗