Region Of Chr Research Articles

Cloning and characterization of the mouse interleukin enhancer binding factor 3 (Ilf3) homolog in a screen for RNA binding proteins.

In a screen for RNA-binding proteins expressed during murine spermatogenesis, we have identified a cDNA that encodes a protein of 911 amino acids that contains two copies of the double-stranded RNA-binding motif and has 80% identity with human Interleukin Enhancer Binding Factor 3 (ILF3). Linkage and cytogenetic analyses localized the Ilf3 cDNA to a portion of mouse Chr 9, which shows conserved synteny with a region of human Chr 19 where the human ILF3 gene had been previously localized, supporting that we had cloned the murine homolog of ILF3. Northern analysis indicated the Ilf3 gene is ubiquitously expressed in mouse adult tissues with high levels of expression in the brain, thymus, testis, and ovary. Polyclonal antibodies detected multiple protein species in a subset of the tissues expressing Ilf3 RNA. Immunoreactive species are present at high levels in the thymus, testis, ovary, and the spleen to a lesser extent. The high degree of sequence similarity between the mouse ILF3 protein and other dsRNA binding motif-containing proteins suggests a role in RNA metabolism, while the differential expression indicates the mouse ILF3 protein predominantly functions in tissues containing developing lymphocyte and germ cells.

Genetic mapping of the whirler mutation.

The whirler (wi) mutation on mouse Chromosome (Chr) 4 results in an autosomal recessive neuroepithelial deafness and vestibular dysfunction exhibited as a characteristic shaker-waltzer behavior (deafness, circling, and head-bobbing). We have constructed a genetic linkage map across the wi region in both an interspecific [(wi/wi x CAST/Ei)F1 x wi/wi] backcross (n = 817) and an intraspecific [(wi/wi x CBA/Ca)F1 x wi/wi)] backcross (n = 335). In the interspecific backcross, wi was found to be non-recombinant with Orm1, 0.12 cM distal of D4Mit87 and Ambp, and 0.12 cM proximal of CD301. In the intraspecific backcross, wi was found to be non-recombinant with Orm1 and D4Mit244, 0.3 cM distal of Mup1, and 0.6 cM proximal of Tnc. We also report a family from the interspecific backcross that shows evidence of multiple recombinations across the region of mouse Chr 4 around the wi locus. These rearrangements appear specific to both the region and the family.

Identification of genes within the Krd deletion on mouse chromosome 19.

The Krd deletion, Del(19)TgN8052Mm, was generated by a non-targeted transgene insertion into the distal region of mouse Chr 19(Keller et al. 1994). The length of the deletion was estimated to beapproximately 5 cM from the recombination rate of flanking mark-ers. Three deleted genes were identified in the original report:Pax2, Scd1, and the coat color mutation pale ear (ep).The kidney and retinal degeneration observed in Krd/+ hetero-zygotes includes early development of renal cysts, a low frequencyof unilateral or bilateral agenesis of the kidney, and disorganiza-tion of the retinal cell layers (Keller et al. 1994). Retinal develop-ment is disrupted owing to the absence of a small population ofprecursor cells (Otteson et al. 1998). We originally suggested thatthese abnormalities were caused by haploinsufficiency for thepaired box domain transcription factor gene Pax2, which is in-volved in the early stages of organogenesis of the kidney and retina(Dressler 1996). This prediction was confirmed by the identifica-tion of human patients with point mutations in PAX2 and abnor-malities similar to the Krd mouse (Sanyanusin et al. 1995; Schi-menti et al. 1997) and by characterization of a point mutation in themouse (Favor et al. 1996). Mice homozygous for the Krd deletiondo not survive to birth and appear to be lost at an early, pre-implantation stage (Keller et al. 1994).There is currently renewed interest in mouse chromosomaldeletions because of their utility as sensitized background for mu-tagenesis (Davis and Justice 1998). To evaluate the potential of theKrd deletion for use in a sensitized mutation screen, we haveanalyzed several genes and ESTs mapped to this region of Chro-mosome (Chr) 19. To determine whether these genes were locatedwithin the deletion, we tested the ability of the deletion-bearingchromosome to transmit each locus in a cross between C57BL/6J-Krd/+ mice and strain SPRET/Ei or CAST/Ei. The Krd/+ offspringof these crosses were identified by PCR with primers derived fromthe transgene (Keller et al. 1994). Failure to transmit a C3H orC57BL/6J allele along with the Krd transgene marker indicatesthat the locus is deleted from the Krd chromosome (Keller et al.1994). Genomic DNA from the Krd/+ offspring was analyzed byuse of polymorphic differences between the parental strains (Table1). Five genes were examined by Southern blotting: Fgf8, Wnt8b,Tlx1, Pitx3 and Nkx2-3.Four of these failed to be transmitted fromthe Krd chromosome (Table 1). The Cmoat gene encoding an iontransport protein was demonstrated to be deleted by a single-stranded conformational polymorphism (SSCP) assay. The othergenes and ESTs that were tested were observed to be transmittedto the Krd/+ F

Identification of a novel inflammation-protective locus in the Fischer rat.

Inbred LEW/N rats are relatively susceptible, while histocompatible inbred F344/N rats are relatively resistant to development of a wide variety of inflammatory diseases in response to a range of pro-inflammatory stimuli. In a LEW/N vs. F344/N F2 intercross, we identified a quantitative trait locus (QTL) on Chr 10 that protects in a dominant fashion against the exudate volume component of innate inflammation in the F344/N rat, as well as a suggestive QTL on Chr 2 near the Fibrinogen cluster region. The exudate volume linkage region on Chr 10 may be similar to one of the multiple regions found to link to inflammatory arthritis phenotypes in other crosses. The suggestive linkage on Chr 2 has not been previously reported and does not seem to contribute to this phenotype in the same manner as the QTL on Chr 10. These findings are consistent with the hypothesis that the innate exudate volume trait is a sub-phenotype of more complex inflammatory phenotypes, such as arthritis, and genes within the Chr 10 linkage region could account for differences in this non-specific acute phase component of the inflammatory response. Since the rat Chr 10 exudate volume linkage region we have identified is syntenic with a region of human Chr 17 that has been shown to link to a variety of autoimmune/inflammatory diseases, including insulin-dependent diabetes mellitus, multiple sclerosis, and psoriasis, identification of genes within this linkage region will shed light on genes relevant to the earliest inflammatory component and to susceptibility and resistance to such human autoimmune/inflammatory diseases.

Genetic mapping of eight SH3 domain genes on seven mouse chromosomes.

The process of screening cDNA expression libraries with phageoptimized peptide ligands, termed cloning of ligand targets (COLT), was recently used to isolate a series of SH3 domaincontaining proteins (Sparks et al. 1996). Among the 18 SH3 domain-containing proteins identified, nine were previously unreported from mouse. The structures of seven of the proteins whose genes are mapped in this study are diagrammed in Fig. 1. The function of many of the mouse proteins is being actively pursued by many laboratories. Three of the proteins, SH3P4, SH3P8, and SH3P14, are highly related in structure and have been discovered to bind synaptojanin and dynamin, and to be involved in endocytosis (de Heuvel et al. 1997; Ringstad et al. 1997). This family of proteins, which has also been discovered in human (Giachino et al. 1997), has been termed endophilin 1, 2, and 3. SH3P8 was also identified as a gene fused to MLL in human acute myeloid leukemia (So et al. 1997) and as a protein that binds to the Gag protein of murine leukemia viruses in a yeast two-hybrid screen (W. Kim, T. Torrey, H. Morse, unpublished observations). SH3P9, renamed amphiphysin II because of its strong similarity to amphiphysin, has been shown to be a component of the endocytic machinery (Butler et al. 1997; Ramjaun et al. 1997) as well as the cytoskeleton, where it may regulate the c-Abl tyrosine kinase (Kadlec and Pendergast 1997). SH3P12 has been observed to interact with c-Cbl in cells where it may play a role in both signal transduction pathways and regulation of the cytoskeleton (Ribon et al. 1998). To learn more about the genes for the seven novel mouse proteins, we set out to map their chromosomal locations. Two sets of multilocus genetic crosses were analyzed for inheritance of the mouse genes encoding the SH3 family genes: (NFS/N or C58/J × M. m. musculus) × M. m. musculus (NMM and CMM; Kozak et al. 1990) and (NFS/N x M. spretus) × M. spretus or C58/J (NSS and NSC; Adamson et al. 1991). Probes were prepared by polymerase chain reaction (PCR) from the nine cDNA clones, seven of which have been deemed full-length (Sparks et al. 1996), and used in blots of restriction enzyme digests of genomic DNA. Inheritance patterns were described for eight polymorphic fragments identified by the seven different probes. Restriction fragments used to identify specific loci are given in Table 1. Seven loci were typed in the M. spretus crosses and six loci in the M. m. musculus crosses. Comparisons of the inheritance patterns of these fragments with those of over 1200 loci previously typed and mapped in these crosses showed that eight loci could be positioned on seven chromosomes. Two genes were mapped to Chromosome (Chr) 19, but they were separated by more than 20 cM. The recombination data used to derive the map locations are given in Table 2. In all but one case, all restriction fragments identified by a single probe could be mapped to the same locus. The exception, probe SH3P13, identified loci on two mouse chromosomes, Chrs 2 and 7. The two corresponding loci, Sh3d2c1 and Sh3d2c2, were identified in both sets of crosses, indicating that neither represented a species-specific pseudogene. Previous data have shown that the human homolog of this SH3 domain gene, originally termed SH3GL3, is located at 15q24 (Giachino et al. 1997). One of the mouse loci identified by this probe, Sh3d2c2, mapped to a region of Chr 7 homologous to 15q21-26, identifying it as the mouse homolog of human SH3GL3. The nature of the second locus, Sh3d2c, remains to be determined. Human map locations have also been defined for Sh3d2a and Sh3d2b. The homolog of Sh3d2a (SH3GL2) was mapped to 9p22, which is consistent with its position on mouse Chr 4. We previously reported the map location for Sh3d2b on mouse Chr 17 (Torrey et al. 1998), consistent with the human location for SH3GL1 on 19p13.3. Finally, another SH3 domain gene, Amph (amphiphysin), maps to mouse Chr 13 and human 7p14-p13 (Jenkins et al. 1995). None of the other genes have been mapped in human, although mouse map locations predict positions for SH3D4 and SH3D5 on human chromosomes 8p21-23 and 10q respectively. Since map locations for Dbn1l and Sh3d3 place them in regions with homology to two or more human chromosomes, we attempted to make

Recurrent non-reciprocal translocations of chromosome 5 in primary T(12;15)-positive BALB/c plasmacytomas.

The majority of inflammation-induced peritoneal BALB/c plasmacytomas (approximately 90%) harbor a balanced T(12;15) chromosomal translocation that deregulates the expression of the proto-oncogene c-myc. Recent evidence suggests that the T(12;15) is an initiating tumorigenic mutation that occurs in early plasmacytoma precursor cells. However, plasmacytomas take a long time to develop (average tumor latency approximately 220 days), which suggests that additional tumor progression events may be required to complete oncogenesis. We hypothesized that such tumor progression events may take the form of secondary chromosomal aberrations that can be detected by spectral karyotyping (SKY). We screened the entire chromosome complement of 18 primary BALB/c plasmacytomas carrying the T(12;15) and found in nine tumors (50% recurrence) secondary cytogenetic aberrations that involved bands D, E and F chromosome (Chr) 5. The Chr 5D-F rearrangements were manifested predominantly as unbalanced translocations with various partner chromosomes. This finding led us to propose the existence of an important plasmacytoma progression locus in the central region of Chr 5, which presumably becomes involved in peritoneal plasmacytoma development by promiscuous chromosomal translocations.

The original shaker-with-syndactylism mutation (sy) is a contiguous gene deletion syndrome.

Tests for allelism among mice with four different mutant alleles at the shaker-with-syndactylism locus on mouse Chromosome (Chr) 18 provide evidence that the original radiation-induced mutation, sy, is a deletion including at least two genes associated with distinct phenotypes. Mice homozygous for sy have syndactylous feet and other skeletal malformations, are deaf, and exhibit abnormal behavior characteristic of vestibular dysfunction. Two less severe spontaneous mutations, shown to be allelic with sy, cause syndactylism when homozygous (hence named fused phalanges, sy(fp) and sy(fp-2J)), but do not affect hearing and behavior. Here we describe a third spontaneous mutation allelic with sy that does not affect foot morphology (hence named no syndactylism, sy(ns)), but that does cause deafness and balance defects when homozygous. Complementation test results indicate that sy(fp) and sy(fp-2J) are alleles of the same gene, but that sy(ns) is an allele of a different gene. The original sy mutation, therefore, includes both of the genes defined by these three spontaneous mutations. Typing of DNA markers in sy/sy mice revealed a deletion of approximately 1 cM in the sy region of Chr 18, including D18Mit52, D18Mit124, D18Mit181, and D18Mit205. The genetic relationships described here will aid in positional cloning efforts to identify the genes responsible for the disparate phenotypes associated with the sy locus.

Germ cell-specific enhancer activity of a repeated element in a variable region of the mouse genome.

We recently described a complex genetic structure on mouse chromosome 8, a region of the murine genome in which genetic rearrangements frequently occur. A large repeated element specific to this chromosome was found to overlap with one of the cadherin genes (Cad11). An additional degree of complexity became apparent with the identification, in a subset of laboratory strains of mice, of a retrogene integrated into one of the repeated units. Designated Sycp1-ps2, it originated from the early meiotic gene encoding Synaptonemal Complex Protein 1. We now report that, among wild Mus species in which the retrogene is not present, this region of Chr 8 shows a high degree of variability. Sequence analysis showed that integration of Sycp1-ps2 created a 5' transcription initiator element. Transcription of the pseudogene in the testis was directly demonstrated. A germ cell-specific enhancer activity was localized within a 1117 bp region of the repeat, which was sufficient to direct the expression of reporter genes in transgenic mice to late meiotic and post-meiotic spermatogenic cells.

Sex-restricted non-Mendelian inheritance of mouse chromosome 11 in the offspring of crosses between C57BL/6J and (C57BL/6J x DBA/2J)F1 mice.

We report on the observation of sex-restricted, non-Mendelian inheritance over a region of mouse Chromosome (Chr) 11, occurring in the offspring of crosses between two commonly used Mus musculus-derived inbred strains, C57BL/6J and DBA/2J. In the surviving backcross progeny of reciprocal matings between (C57BL/6J x DBA/2J)F1 hybrids and the C57BL/6J parental strain, we observed the preferential appearance of C57BL/6J alleles along a region of Chr 11. The deviation from Mendelian predictions was observed only in female offspring from both reciprocal backcrosses, and not in males from either cross. The sex-specificity of the observed non-Mendelian inheritance points to an explanation based on embryonic or neonatal lethality. Our data add to previously obtained evidence for a Chr 11 locus or loci with sex-specific and allele-specific effects on viability.

Murine Stim1 maps to distal chromosome 7 and is not imprinted.

STIM1 (GOK) maps to a region of human Chromosome (Chr) 11p15.5 that is implicated in several embryonal tumors, and some evidence indicates that STIM1 may have a growth suppressor role in rhabdomyosarcoma. In this study we have mapped the murine homolog, Stim1, to the same position as Hbb on distal mouse Chr 7. This region is separated by 20 cM from the region of distal Chr 7 that contains Igf2, H19, and other imprinted genes. Using strain-specific polymorphisms, we have shown that Stim1 is expressed from both parental alleles in fetal and neonatal mouse tissues. Similar analyses of human Wilms' tumor and normal kidney tissues demonstrated biallelic expression of STIM1 in the majority of samples. These data demonstrate that Stim1 expression is not regulated by genomic imprinting in either mouse or human tissues. Thus, if STIM1 is a tumor suppressor at 11p15.5, loss of expression is not due to imprinting effects.

A deletion in the myostatin gene causes the compact (Cmpt) hypermuscular mutation in mice.

A deletion in the myostatin gene causes the compact (Cmpt) hypermuscular mutation in mice.

Chromosomal locations of the mouse fatty acid oxidation genes Cpt1a, Cpt1b, Cpt2, Acadvl, and metabolically related Crat gene.

Mitochondrial beta-oxidation of long-chain fatty acids (LCFA) is essential for mammalian life. Because portions of this metabolic pathway are composed of enzymes that are coordinately regulated and share structural and functional similarities, we evaluated five of these enzyme genes for possible chromosomal linkages. Regulation of LCFA catabolism influences cell signal pathways and apoptosis, as well as energy production from LCFA. Partial cDNA fragments of the mouse mitochondrial proteins carnitine acetyltransferase (Crat), very-long-chain acyl coenzyme A dehydrogenase (Acadvl), the liver and muscle isoforms of carnitine acyltransferase I (Cpt1a and Cpt1b respectively), and a genomic PCR product of mitochondrial protein carnitine acyltransferase II (Cpt2) were used in a previously established mapping panel to determine their chromosomal locations. No pseudogenes were detected for any of the genes in Mus musculus, and all of the genes mapped to different chromosome locations, including the tissue-specific isoforms of carnitine palmitoyltransferase. Crat mapped to Chromosome (Chr) 2, at a position approximately 18 cM from the centromere and 2 cM proximal to the gene Ass1. Acadvl mapped to the middle of Chr 11, 8.3 cM distal to Il4 and 2.8 cM proximal to Mpmv2. Cpt1a mapped to the centromeric region of Chr 19, 8.7 cM proximal to Pomc-ps1. Cpt1b mapped to Chr 15, 4.9 distal to Gpt1 and 3.5 cM proximal to Wnt1. Cpt2 mapped to Chr 4 near the locus Pmv19.

Chromosomal localization and characterization of the stannin (Snn) gene.

Stannin is a protein that has been localized to trimethyltin-sensitive cell populations, and evidence suggests it plays a role in the toxic effects of organotins. In this study, we have isolated a mouse stannin genomic clone and have characterized the gene's intron-exon organization, promoter region, and chromosomal location. We have also isolated a partial human stannin cDNA clone and analyzed the open reading frame. The mouse genomic clone spans approximately 19 kb and consists of one intron and two exons. The splice site consensus sequence was maintained at all intron-exon junctions. Promoter analysis suggests that two putative promoter sites exist, each containing multiple regulatory elements and transcription factor-binding sites. Fluorescence in situ hybridization analysis localized stannin to mouse Chromosome (Chr) 16 at band A2. This region is homologous to the proximal region of human Chr 16 (16p13) to which stannin has been previously mapped. Sequence analysis revealed that the 264-bp open reading frame was identical between rat and mouse. The human sequence was 98% identical, with two amino acid substitutions near the c-terminal end of the peptide. These data suggest that stannin is highly conserved between species, and its unusual pattern of cellular expression may, in part, be explained via cell-specific promoters.

The Protein Kinase N (PKN) GenePRKCL1/Prkcl1Maps to Human Chromosome 19p12–p13.1 and Mouse Chromosome 8 with Close Linkage to the Myodystrophy (myd) Mutation

Protein kinase N (PKN) is a fatty acid- and Rho-activated serine/threonine protein kinase involved in the regulation of cell motility by association with cytoskeletal components such as neurofilament and α-actinin. We determined the chromosomal location of the human PKN genePRKCL1by fluorescencein situhybridization and by radiation hybrid mapping. The corresponding mouse genePrkcl1was mapped by segregation analysis. We found by FISH thatPRKCL1is localized to chromosome 19p12–p13.1 and, more precisely, by radiation hybrid mapping, about 11 cR from ESTWI-6344in subband 19p12.Prkcl1maps to mouse chromosome 8 betweenD8Mit6andjunb.This region of mouse Chr 8 shows a scrambled syntenic conservation to human chromosomes 4q, 8p, and 19p. As the mouse mutation myodystrophymydhas been mapped to the same region,Prkcl1is a candidate gene formyd.

BAC/YAC contigs from the H2-M region of mouse Chr 17 define gene order as Znf173-Tctex5-mog-D17Tu42-M3-M2.

A yeast artificial chromosome (YAC) contig from the C57BL/6 (H2(b)) mouse was created from the major histocompatibility complex (Mhc, H2 in mouse) class Ib subregion, H2-M. It spans approximately 1.2 megabase (Mb) pairs and unites the previous >1.5-Mb YAC contigs (Jones et al. 1995) into a single contig, which includes 21 Mhc class I genes distal to H2-T1. A bacterial artificial chromosome (BAC) contig from the 129 (H2(bc)) mouse, spanning approximately 600 kilobases, was also built from Znf173 (Afp, a gene for acid finger protein), through Tctex5 (t-complex testis expressed-5) and Mog (myelin oligodendrocyte glycoprotein), to H2-M2. Twenty-four sequence-tagged site (STS) markers were newly developed, and 35 markers were mapped in the YAC/BAC contigs, which define the marker order as Cen - Znf173 - Tctex5 - Mog - D17Tu42 - D17Mit232 - H2-M3 - D17Leh525 - H2-M2 - Tel. The gene order of Znf173 - Tctex5 - Mog - D17Tu42 is conserved between mouse and human, showing that the middle H2-M region corresponds to the subregion of the human Mhc surrounding HLA-A.

Structural organization and chromosomal localization of the human Na,K-ATPase beta 3 subunit gene and pseudogene.

We have cloned and characterized the Na,K-ATPase beta 3 subunit gene (ATP1B3), and a beta 3 subunit pseudogene (ATP1B3P1), from a human PAC genomic library. The beta 3 subunit gene is > 50 kb in size and is split into 7 exons. The exon/intron organization of the beta 3 subunit gene is identical to that of the Na,K-ATPase beta 3 subunit gene, indicating that these two genes evolved from a common evolutionary ancestor. Comparison of the promoter region of the human and mouse beta 3 subunit gene reveals a high degree of homology within a 300-bp segment located immediately upstream of the translation start site, suggesting that control elements that serve to regulate the cell-specific expression of the beta 3 subunit gene are likely to be located within this conserved region. Dot blot analysis of beta 3 subunit transcripts revealed expression within virtually all human tissues, while in situ hybridization showed expression of beta 3 mRNA in both neurons and glia of rat brain. Fluorescence in situ hybridization with PAC DNA clones localized ATP1B3 to the q22-->23 region of Chromosome (Chr) 3, and the beta 3 pseudogene to the p13-->15 region of Chr 2.

Association of a redefined proximal mouse chromosome 11 imprinting region and U2afbp-rs/U2af1-rs1 expression

Mice with maternal and paternal disomy for chromosome 11 (Chr 11) show growth retarded and overgrowth phenotypes, respectively, which can be attributed to genomic imprinting. Previous studies have defined the region of Chr 11 responsible (the Chr 11 imprinting region) as lying proximal to the T30H translocation breakpoint at the borders of G-bands 11B1.2 and 11B1.3. Evidence is presented here with two new translocations, T57H and T41Ad, which sequentially reduce the size of the imprinting region and locate it proximal to the T41Ad breakpoint in G-band 11A3.2. It therefore lies close to the centromere. The imprinted gene, U2af1-rs1, is known to be located within the original region and has been regarded as a candidate for the imprinting effects. Meiotic and mitotic chromosome FISH analysis, together with U2af1-rs1 expression studies are now described which show that the gene lies within the newly defined imprinting region and that its expression levels relate to the presence/absence and number of functional paternal alleles. U2af1-rs1 therefore remains a candidate gene for the Chr 11 imprinting effects. However, another recently reported imprinted gene, Meg1/Grb10, that lies within the region is also a good candidate, as it encodes a growth factor receptor. Meg1/Grb10 maps about 15 cM from U2af1-rs1 and is separated by conserved regions showing homology with two different human chromosomes. For these reasons, and because the two human homologues of U2af1-rs1 and Meg1/Grb10 also lie on different chromosomes, it would seem likely that the two genes identify two distinct imprinting domains within the small proximal region of mouse Chr 11.

Molecular Cloning and Characterization of a cDNA, CHEMR1, Encoding a Chemokine Receptor With a Homology to the Human C-C Chemokine Receptor, CCR-4

AbstractChemokines refer to a rapidly expanding family of small cytokines whose primary function is recruitment of leukocytes to inflammatory sites. These are known to bind to seven-transmembrane-domain containing receptors. A cDNA clone, CHEMR1, resembling the typical G protein-coupled receptor, was isolated from a mouse cytotoxic T-lymphocyte (CTL) library. Northern blot analysis in mouse cell lines suggests that its expression is found in a variety of cells, including T cells, B cells, and macrophages. The CHEMR1 gene Scya3r2 is a single-copy gene whose open reading frame may be in a single exon and maps to the distal region of mouse Chr 9 where the mouse macrophage inflammatory protein-1α (MIP-1α) receptor gene Scya3r and two related C-C chemokine receptor-like genes reside. Amino acid sequence comparison shows that CHEMR1 is 84% identical to human CCR-4, indicating that CHEMR1 is likely to be a mouse CCR-4. Binding assays using 125I-labeled C-C chemokines in mammalian cells indicated that CHEMR1 did not bind MIP-1α, RANTES, or MIP-1β, whereas CCR-1 binds MIP-1α and RANTES. Our result is different from the reported properties of human CCR-4. This suggests that CHEMR1 may be a receptor for unidentified C-C chemokine or a low-affinity receptor for MIP-1α.

The mouse homolog of FRG1, a candidate gene for FSHD, maps proximal to the myodystrophy mutation on chromosome 8.

The human autosomal dominant neuromuscular disorder facioscapulohumeral muscular dystrophy (FSHD) is associated with deletions within a complex tandem DNA repeat (D4Z4) on Chromosome (Chr) 4q35. The molecular mechanism underlying this association of FSHD with DNA rearrangements is unknown, and, thus far, no gene has been identified within the repeat. We isolated a gene mapping 100 kb proximal to D4Z4 (FSHD Region Gene 1:FRG1), but were unable to detect any alterations in total or allele-specific mRNA levels of FRG1 in FSHD patients. Human Chr 4q35 exhibits synteny homology with the region of mouse Chr 8 containing the gene for the myodystrophy mutation (myd), a possible mouse homolog of FSHD. We report the cloning of the mouse gene (Frg1) and show that it maps to mouse Chr 8. Using a cross segregating the myd mutation and the European Collaborative Interspecific Backcross, we showed that Frg1 maps proximal to the myd locus and to the Clc3 and Ant1 genes.

Mapping of two different alpha-1,2-fucosyltransferase genes to rat chromosome 1q22-q31.

and egam2e 1Neu show similar phenotypes although there are differences in the degree of the PGAM activity elevation. Linkage analyses localized Pgam2e 1Neu to the distal region of Chr 4 between markers D4Mit134 and D4Mit54 (Fig. 1). Thus, a second locus for increased PGAM activity in the mouse genome has been identified. We have recovered and maintained a total of 15 mutations with altered PGAM activity in an extensive series of mutagenesis experiments. Further studies will be undertaken to determine allelism with the Pgam structural locus as well as with Pgamle or Pgam2e.