Biomedical subjects

H Zha

Publications and source records attributed to H Zha.

28 records · Page 2Linked to original sources

PubMed1993

Linkage map of nine loci defined by polymorphic DNA markers assigned to rat chromosome 13.

A genetic map of nine loci defined by polymorphic DNA markers was created using a single cross of F344/N and LEW/N rats. The markers contained polymorphic simple sequence repeats identified in five genes, renin (Ren), cardiac troponin T (Tnnt3), synaptotagmin (Syt2), Na+,K(+)-ATPase catalytic subunit (Atp1a2), and the Asp-, Gly-, Glu-, and Leu-tRNA gene cluster (Trnegl), as well as four anonymous DNA segments. Analysis of the segregation of the alleles of these markers in F2 intercross progeny of F344/N and LEW/N rats indicated the following locus order and distances between pairs of loci: D13N1-5 cM-Ren-1 cM-Tntt3-0 cM-Syt2-12 cM-D13N2-25 cM-Atp1a2-0 cM-Trnegl-7 cM-D13N3-4 cM-D13N4. Three of the loci, Ren, Trnegl, and Atp1a2, have previously been assigned to rat chromosome 13. Except for Ren, none of the loci have previously been mapped by linkage analysis. The markers for these loci were characterized in a total of 13 inbred rat strains (F344/N, LEW/N, LOU/MN, WBB1/N, WBB2/N, MR/N, MNR/N, ACI/N, SHR/N, WKY/N, BN/SsN, BUF/N, and LER/N) and were found to be highly polymorphic, with two to eight alleles detected for each marker. These markers expand the genetic map of the rat and should be valuable tools for future genetic studies. An examination of human and mouse comparative map information for all loci assigned to rat chromosome 13 shows significant synteny conservation with the q arm of human chromosome 1 and the distal portion of mouse chromosome 1.

Animals↗

PubMed1993

Map of seven polymorphic markers on rat chromosome 14: linkage conservation with human chromosome 4.

Seven polymorphic markers identified by polymerase chain reaction (PCR) amplification, including markers for six genes--DRD1L (dopamine receptor, D1-like-2), GLUKA (glucokinase), PF4 (platelet factor 4), ALB (albumin), AFP (alpha-fetoprotein), and BSP (bone sialoprotein)--and one anonymous locus (D14N52), were mapped to a single 67-cM linkage group with F2 intercross progeny of F344/N and LEW/N inbred rat strains. Two of these markers, ALB and AFP, have previously been assigned to rat Chromosome (Chr) 14, allowing assignment of this entire linkage group. Five of the markers--DRD1L, PF4, ALB, AFP, and BSP--have been physically mapped to a large region of human Chr 4 encompassing the p arm and the q arm to band q28. Homologs of two of the markers, ALB and AFP, have been mapped to Chr 5 in the mouse. Comparison of human Chr 4 with the homologous regions on Chr 14 of the rat and Chr 5 of the mouse indicated that linkage conservation with human Chr 4 extends over a greater region in the rat than in the mouse. The markers described here were found to be highly polymorphic in twelve inbred strains (F344/N, LEW/N, ACI/N, BUF/N, BN/SsN, LOU/MN, MNR/N, MR/N, SHR/N, WBB1/N, WBB2/N, and WKY/N). These polymorphic markers should be useful in genetic linkage studies of important phenotypes in rats.

Animals↗

PubMed1993

Genetic map of seven polymorphic markers comprising a single linkage group on rat chromosome 5.

Seven polymorphic markers comprising a single linkage group were assigned to rat Chromosome (Chr) 5 by linkage analysis of the progeny of an F2 intercross of Fischer (F344/N) and Lewis (LEW/N) inbred rats. Three genes, alpha-L-fucosidase 1 (FUCA1), mitochondrial superoxide dismutase (SOD2), and glucose transporter (GLUT1), were mapped by restriction fragment length polymorphism (RFLP) analysis. Two genes, glucose transporter (GTG3) and elastase II (ELAII), one pseudogene for alpha tubulin (TUBAPS), and one sequence related to the 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase gene (PFKFBP1-related sequence) were mapped by simple sequence repeat (SSR) polymorphism analysis. The loci are in the following order: SOD2, GTG3/GLUT1, FUCA1, ELAII/PFKFBP1-related sequence, and TUBAPS. This linkage group covered 68.3 cM of rat Chr 5. The SSR markers were highly polymorphic in 13 inbred rat strains (SHR/N, WKY/N, MNR/N, MR/N, LOU/MN, BN/SsN, BUF/N, WBB1/N, WBB2/N, ACI/N, LER/N, F344/N, and LEW/N). These markers, located on rat Chr 5, will be useful in genetic studies of inbred rats.

Animals↗

PubMed1993

Genetic mapping of the athymic nude (RNU) locus in the rat to a region on chromosome 10.

The nude trait in the rat is transmitted in an autosomal recessive manner and is associated with thymic aplasia, T-cell deficiency, and hairlessness. Congenic rats homozygous for the RNU (Rowett nude) locus are important models in the study of inflammatory disease, tumor growth, and transplant rejection. The RNU locus has not been previously mapped, and the nature of the gene product is unknown. To determine the map location of this gene, a single F344.rnu/rnu (athymic nude congenic Fischer rat) male congenic rat was bred with 3 LEW/N (NIH stock Lewis rat) female rats to produce F1 progeny. Twelve F1 brother-sister breeding pairs were established. Forty-nine phenotypically nude F2 offspring (198 total) were obtained. Linkage analysis done on F2 DNA revealed highly significant cosegregation between the nude phenotype and eight polymorphic markers located on Chromosome (Chr) 10. The tightest linkages were with: MYH3 (embryonic, skeletal myosin heavy chain) and SHBG (sex hormone-binding globulin), giving 2 point lod scores of 20.2, and 20.0, respectively. The map order and map distances, determined by multipoint linkage calculations, were: RR24-(16.1 cM)-MYH3-(3.5 cM)-SHBG-(4.7 cM)-RNU-(11.9 cM)-F16F2-(24.1 cM)-CLATP (citrate lyase ATPase)-(2.4 cM)-ACE (angiotensin converting enzyme)/PPY (pancreatic polypeptide)-(14.1 cM)-RR1023. The position of the RNU locus in the rat corresponds closely with that of the recently reported nu locus in the mouse. This finding suggests that the nude phenotype in the rat and the mouse arise from defects in homologous genes.

Animals↗

PubMed1993

Linkage map of seven polymorphic markers on rat chromosome 18.

A genetic linkage map of seven polymorphic markers was created with F2 intercross progeny of F344/N and LEW/N rats and assigned to rat Chromosome (Chr) 18. Five of the markers described were defined by simple sequence length polymorphisms (SSLPs) associated with five genes: transthyretin (TTR), trypsin inhibitor-like protein (TILP), beta 2 adrenergic receptor (ADRB2), olfactory neuron-specific G protein (OLF), and gap junction protein (GJA1). One marker was defined by a restriction fragment length polymorphism (RFLP) detected with a probe for the human colony stimulating factor 1 receptor (CSF1R) gene. The D18N1R locus was defined by an anonymous DNA fragment amplified by the randomly amplified polymorphic DNA (RAPD) technique with a single short primer. These seven DNA loci formed a single genetic linkage group 30.4 cM in length with the following order: TTR-6.8 cM-D18N1R-9.1 cM-TILP-4.3 cM-CSF1R-0 cM-ADRB2-10.2 cM-OLF-0 cM-GJA1. The five SSLP markers were highly polymorphic. In a total of 13 inbred rat strains analyzed (F344/N, LEW/N, LOU/MN, WBB1/N, WBB2/N, MR/N, MNR/N, ACI/N, SHR/N, WKY/N, BN/SsN, BUF/N, and LER/N), three to six alleles were detected for each marker. Remarkable linkage conservation was detected between the region of rat Chr 18 mapped and a region of mouse Chr 18. However, genes associated with these markers have been mapped to three different human chromosomes (Chrs 5, 6, and 18). The markers described here should be useful for genetic mapping studies and genetic monitoring of inbred rat strains.

Alleles↗

PubMed1993

Four polymorphic markers on rat chromosome 12 form a single linkage group.

Four PCR-typable polymorphic markers were mapped to rat chromosome 12 by linkage analysis of F2 intercross progeny of Fischer (F344/N) and Lewis (LEW/N) rat strains. The markers formed a single linkage group, covering 27.7 cM, with the following order and distance between markers: plasminogen activator inhibitor (Planh)--0.0 cM--phosphoenolpyruvate carboxykinase-related sequence 2 (Pepckr2)--15.4 cM--anonymous marker (D12N155)--12.3 cM--serine dehydratase (Sdh). All markers were identified and genotyped by PCR analysis of simple sequence repeats. The gene encoding Planh was previously assigned to rat chromosome 12, which allowed us to assign the entire linkage group to this chromosome. These markers were highly polymorphic in 13 additional inbred rat strains (BUF/N, BN/SsN, WKY/N, MNR/N, LER/N, WBB1/N, WBB2/N, MR/N, LOU/MN, SHR/N, ACI/N, SR/Jr, and SS/Jr). These markers should be useful tools for further genetic studies in rats.

Animals↗

PubMed1993

The origin of the autoimmune disease-resistant LER rat: an outcross between the buffalo and autoimmune disease-prone Lewis inbred rat strains.

The Lewis (LEW) rat strain is highly susceptible to a large number of experimentally induced inflammatory and autoimmune diseases. The Lewis resistant (LER) rat strain, which reportedly arose as a spontaneous mutation in a closed colony of LEW rats, is resistant to many of these disorders. The mechanism of resistance is not yet clear. We report the analysis of 19 simple dinucleotide repeat polymorphisms in 13 rat strains including the LEW/N and LER/N rat strains. The LEW/N and LER/N alleles were the same in only 42% of cases. For all of the other polymorphisms, the LER/N and Buffalo (BUF/N) rat strain alleles were identical. These data provide evidence that the LER strain did not arise as a spontaneous mutation in the LEW strain but is the result of an outcross between the LEW and BUF rat strains. The LER rat strain is now a recombinant inbred rat strain. This information should facilitate the genetic analysis of the loci responsible for resistance to experimental autoimmune disease in the LER rat.

Alleles↗

PubMed1993

Linkage map of 10 polymorphic markers on rat chromosome 2.

Analysis of F2 intercross progeny of inbred F344/N x LEW/N rats led to the assignment of 10 polymorphic PCR-typable markers to rat chromosome 2. The markers form a single linkage group covering 47.9 cM with the following order: D2N1R-D2N28-FGG (gamma fibrinogen)-PKLR (liver and RBC pyruvate kinase)-ATP1A1 (the alpha-1 polypeptide of Na+/K+ transporting ATPase)-HSD3B (hydroxy-delta-5-steroid dehydrogenase)-D2N2R-D2N91-CAMKI (calmodulin-dependent protein kinase II)-D2N35. All but two of the markers (D2N1R and D2N2R) were detected using specific PCR primers flanking dinucleotide repeats. Sequences with dinucleotide repeats associated with five genes (FGG, PKLR, ATP1A1, HSD3B, and CAMKI) were identified in GenBank, and primers were designed to flank these repeats. The PCR primer pairs for three anonymous markers (D2N28, D2N91, and D2N35) were identified by sequencing cloned LEW/N rat genomic DNA containing (CA)n.(GT)n repeats. D2N1R and D2N2R were identified by PCR amplification of genomic DNA with single, nonspecific 10-base oligonucleotide primers. All of the markers were codominant except for D2N1R, D2N2R, and CAMKI, which only amplified from F344/N homozygous and heterozygous rat DNA. The seven codominant markers were highly polymorphic in 10 other inbred rat strains (SHR/N, WKY/N, MNR/N, MR/N, LOU/MN, BN/SsN, BUF/N, WBB1/N, WBB2/N, and ACI/N), suggesting that they will be useful for general mapping studies among these strains. Comparative gene mapping analysis indicated that a portion of the mapped region of rat chromosome 2 exhibits synteny conservation with regions of human chromosome 1 and mouse Chromosome 3.

Animals↗

PubMed1992

Serum factor(s) induced by restraint stress in mice and rats suppresses lymphocyte proliferation.

LACA mice were individually restrained in a specially made cylindrical cage for 10-20 h at room temperature (20 degrees C). Serum obtained from stressed mice was found to suppress normal mouse lymphocyte proliferation induced by concanavalin A, suggesting the presence of a suppressive factor(s) in the stressed serum. Adrenalectomy or injections of naltrexone (1, 10, or 20 mg/kg, ip), just prior to and in the middle of the stress period, did not affect the suppressive activity of serum from mice. However, the suppressive activity was totally abolished by general anesthesia with urethane (1.5 g/kg, ip). These results suggest that adrenal hormones and opiate receptors are not involved in the generation of the suppressive factor(s) and that the central nervous system plays a very important role in this process. SD rats were restrained in a supine position for 20 h at room temperature (20 degrees C) and serum from stressed rats was also found to be able to suppress normal mouse lymphocyte proliferation. A further analysis of "stressed serum" indicated that the suppressive factor(s) was heat stable (56 degrees C, 30 min) and acid stable (pH 3.8), but sensitive to 100 degrees C (3 min), an organic solvent (greater than 60% methanol), and proteinases (trypsin and chymotrypsin). From the measurement of gel filtration (HPLC), the molecular weights of the suppressive factor(s) were 155 and 370 kDa. Taken together, these results indicate that the suppressive factor(s) is a protein with a large molecular weight.

Adrenalectomy↗

PubMed1992

Genetic map of nine polymorphic loci comprising a single linkage group on rat chromosome 10: evidence for linkage conservation with human chromosome 17 and mouse chromosome 11.

Seven genes and two anonymous markers were mapped to a single linkage group on rat chromosome 10 using progeny of an F2 intercross of Fischer (F344/N) and Lewis (LEW/N) inbred rats. Two genes, the neu oncogene or cellular homologue of the viral oncogene erbb2 (ERBB2) and growth hormone (GH) were mapped by Southern blot analysis of restriction fragment length polymorphisms. Five genes, embryonic skeletal myosin heavy chain (MYH3), androgen binding protein/sex hormone binding globulin (SHBG), asialoglycoprotein receptor (hepatic lectin)-1 (ASGR1), ATP citrate lysase (CLATP), and pancreatic polypeptide (PPY), and two anonymous markers, F16F2 and F10F1, were mapped using PCR amplification techniques. The PCR-typable polymorphic markers for the five genes were also highly polymorphic in 10 other inbred rat strains (SHR/N, WKY/N, MNR/N, MR/N, LOU/MN, BN/SsN, BUF/N, WBB1/N, WBB2/N, and ACI/N). These markers should be useful in genetic analysis of traits described in inbred rat strains, as well as in genetic monitoring of such strains. The loci in this linkage group covered 50 cM of rat chromosome 10 with the following order: MYH3, SHBG/ASGR1 (no recombinants detected), F16F2, ERBB2, CLATP, PPY, GH, and F10F1. Comparative gene mapping analysis indicated that this region of rat chromosome 10 exhibits linkage conservation with regions of human chromosome 17 and mouse chromosome 11.

Alleles↗