Assignment of Gpam to distal mouse Chromosome 19 by linkage analysis

Assignment of Gpam to distal mouse Chromosome 19 by linkage analysis Mammalian Genome 9, Brief Data Reports 93 and George Klarmann, Alex Chagovetz, William Carroll, and David Vir- Fth 1/66,1.5±1.5 D19Ucla2 DI9Ucla3 Vldir shup for helpful comments on the manuscript. 0/62 (5.8) 2/52,3.8 ± 2.7 D19Mit29 4/53,7.5±3.6 References D19Mit3l 1. Rowe LB, Nadeau JH, Turner R, Frankel WN, Letts VA, Eppig JT, Ko 5/62,8.1±3.5 MSH, Thurston Si, Birkenmeier EH (1994) Mamm Genome 5, 253-274 D19Ucla4 1/63,1.6±1.6 DI9Mitl4 2. Kemper RR, Ahn ER, Zhang P, Lee MYWT, Rabin M (1992) Genomics 6/55, 10.9± 4.2 14, 205-206 3. Hickey RJ, Malkas LH (1997) Crit Rev Eukaryotic Gene Expr 7, 125-157 D19Mit12 Sitney KC, Budd M, Campbell JL (1989) Cell 56, 599-605 4/55,7.3±3.5 DI9Ucla5 5. Chang LS, Zhao L, Zhu L, Chen ML, Lee MYWT (1995) Genomics 28, 3/63, 4.8 ± 2.7 411-419 DI9Uclal 5/60,8.3±3.6 1/63,x.6 X5.46 DI9Mit4 D19Mitl Gpam 1/63, 1.6± 1. Slcl8a2 Assignment of Gpam to distal mouse 1/65, 1.5 ± 1.5 Pnlip Pnliprpl 0/66 (5.4 D19Mit6 t sc t a + i Chromosome 19 by linkage analysis Fig 1. Mapping of Gpam to mouse Chr 19 in an interspecific backcross 1,2,3 l ' ' 3 Carrie L. Welch, * Yu-Rong Xia, 2 [(C57B 1/6J x Mus spretus)F 1 x C57BL/6J]. The chromosome is drawn to 2,3 Peter A. Edwards, 1 '3 '4 Aldons J. Lusis,'' scale with the centromere at the top and the distance of the most distal '3'4 marker from the centromere indicated at the bottom (cum, in centiMor- Johan Ericsson 1 gans). The ratios of the number of recombinants to the total number of informative mice and the recombination frequencies ± standard errors (in 'Department of Medicine, University of California, centiMorgans), for each pair of loci, are indicated to the left of the chro- Los Angeles, California 90095, USA mosome. For pairs of loci that cosegregate, the upper 95% confidence 2Department of Microbiology and Molecular Genetics, University of interval is shown in parentheses. Loci are linked with lod scores greater California, Los Angeles, California 90095, USA than 7.0. Ucla markers were reported in Warden et al. [1] or are unpub- 3 Molecular Biology Institute, University of California, lished data. References for other linked loci can be obtained from the Los Angeles, California 90095, USA Mouse Genome Database [2]. 4Department of Biological Chemistry, University of California, Los Angeles, CA 90095, USA Received: / Accepted: entiation factor-1 (ADD1)/sterol regulatory element-binding pro- tein-1 (SREBP-1) [7]. Thus, regulation of gene expression by Species: Mouse ADD 1/SREBP-1 may play a role not only in cholesterol homeo- Locus name: Glycerol -3-phosphate acyltransferase, mitochondrial stasis and fatty acid synthesis but also glycerolipid synthesis. Locus symbol: Gpam We have mapped the mouse mitochondrial GPAT gene Map position: Chromosome (Chr) 19, centromere-D19Mit12-(7.3 (Gpam) to Chr 19 using linkage analysis. The segregation pattern ± 3.5 cM)-D19Ucla5-(4.8 ± 2.7 cM)-D19Ucla1-(8.3 ± 3.6)- of a Gpam HindIIl variant among 66 backcross mice revealed no D19Mit4-(1.6 ± 1.6 cM)-Gpam, D19Mit1-(1.6 ± 1.6)-SlcJ8a2- recombination between Gpam and the microsatellite marker (1.5 ± 1.5 cM)-Pnlip, Pnliprpl-(1.6 ± 1.6)-D19Mit6 (Fig. 1). D19Mit1. The detection of a single hybridizing M. spretus frag- Method of mapping: Linkage analysis was performed with a panel ment on Southern blots is consistent with the existence of a single of 67 progeny derived from a [(C57BL/6J x Mus spretus) F, x structural gene for GPAT. On the basis of comparative maps of C57BL/6J] interspecific backcross [1]. mouse and human chromosomes, the human homolog of Gpam is Database deposit information: Mouse Genome Database acces- likely to reside on Chr l0g24-q26 [2]. sion number MGD-JNUM-41604 [2]. Allele detection: An HindIII variant was identified and used to Acknowledgments: This work was supported in part by the Laubisch Fund score the presence or absence of a single 6.0-kb M. spretus- (PAE) and National Institutes of Health grant HL30568 (A.J. Lusis and specific fragment in the backcross mice. P.A. Edwards). J. Ericsson is a recipient of an American Heart Association, Discussion: Glycerol-3-phosphate acyltransferase (GPAT), which Greater Los Angeles Affiliate post-doctoral fellowship. catalyzes the initial and committing step in glycerolipid biosyn- thesis, has been predicted to play a pivotal role in the regulation of cellular triacylglycerol and phospholipid levels. Two mammalian References forms of GPAT have been identified on the basis of localization to 1. Warden CH, Mehrabian M, He K-Y, Yoon M-Y, Diep A, Xia Y-R, Wen either the endoplasmic reticulum or mitochondria [3]. Mitochon- P-Z, Svenson KL, Sparkes RS, Lusis AJ (1993) Genomics 18, 295-307 drial GPAT is highly expressed in lipogenic tissues such as liver 2. Mouse Genome Database (MGD). Mouse Genome Informatics Project, and adipose tissue [4]. In animal studies, fasting/refeeding and The Jackson Laboratory, Bar Harbor, Maine. World Wide Web administration of insulin caused a dramatic induction of GPAT [4]. (URL: August 1997 Consistent with these observations, putative carbohydrate- 3. Bell RM, Coleman RA (1983) In The Enzymes, PD Boyer, ed (New responsive sequences were identified in the proximal promoter of York, NY: Academic Press, Inc) pp 87-111 the murine cDNA [5,6]. We have recently demonstrated respon- 4. Shin D-G, Paulauskis JD, Moustaid N, Sul HS (1991) J Biol Chem 266, siveness of the GPAT gene to adipocyte determination and differ- 23834-23839 Yet S-F, Lee S, Hahm YT, Sul HS (1993) Biochem 32, 9486-9491 * Present address: Division of Molecular Medicine, Department of Medi- 6. Jerkins AA, Liu WR, Lee S, Sul HS (1995) J Biol Chem 270, 1416- cine, Columbia University, PH8E-101, 630 West 168th Street, New York, NY 10032, USA. 7. Ericsson J, Jackson SM, Kim JB, Spiegelman BM, Edwards PA (1997) Correspondence to: Welch at Columbia University J Biol Chem 272, 7298-7305 Mammalian Genome Springer Journals

Assignment of Gpam to distal mouse Chromosome 19 by linkage analysis

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