Inherited differences in mouse kidney carnosinase activity

Carnosinase is a peptidase which cleaves B-alanyl-l-histidine (carnosine) and closely related dipeptides. Its activity in kidney cytosol of various mouse strains varies more than 50-fold. The highest activity occurs in random-bred CD-1 and inbred NZB/BINJ mice, while it is barely detectable in BALB/cJ, C57BL/6J, and AU/SsJ among others. Carnosinase is immunologically and enzymologically identical in all high-activity strains. This is the first report of quantitative interstrain differences in carnosinase activity. No other peptidase activity has been reported which exhibits the same strain distribution shown here. In matings and backcrosses between the NZB/BINJ and the BALB/cJ strains, the levels of kidney carnosinase activity in the progeny behave as a classical Mendelian trait.     

Variation in alpha-L-fucosidase properties among 28 inbred mouse strains: Six strains have high enzyme activity and heat-stabile enzyme with a variant pH-activity curve; twenty-two strains have low activity and heat-labile enzyme

Alpha-L-fucosidase in tissues of 28 inbred mouse strains varied with respect to three properties: high or low heat stability, a pH-activity curve with high or low relative activity at pH 2.8, and high or low activity. Alpha-L-fucosidase from six strains (A/J, BDP/J, LP/J, P/J, SEA/GNJ, and 129/J) had high heat stability, high pH 2.8 relative activity, and high activity, whereas the other 22 strains all had low heat stability, low pH 2.8 relative activity, and low activity. The heat-stability difference was seen in all organs tested (brain, liver, kidney, spleen, heart, skeletal muscle, lung, and testis) for two heat-stabile strains (P/J and 129/J) and four heat-labile strains (C57 BL/6J, C3H/HeJ, DBA/2J, and BALB/cJ) studied in detail. The findings suggested that two structural variants of alpha-L-fucosidase, probably genetically determined, exist in these 28 inbred mouse strains, although the presence of linkage disequilibrium between alleles of tightly linked structural and regulatory genes could not be excluded.This work was supported by grants from the National Institutes of Health (NS-15281 and NS-11766), the Muscular Dystrophy Association (H. Houston Merritt Clinical Center for Muscular Dystrophy and Related Diseases), the March of Dimes Birth Defects Foundation, and a generous gift from the Alexander Rapaport Foundation.     

Loss ofHindIII cleavage sites in thed-amino acid oxidase gene in some inbred strains of mice

Summary d-Amino acid oxidase cDNA was amplified by a polymerase chain reaction using RNA extracted from the mouse kidney. When digested withHindIII, the cDNAs of the BALB/c and ddY/DAO^– mice were cleaved into two fragments whereas the cDNA of the ddY/DAO⁺ mice was not. Sequencing revealed that nucleotide-471 of the cDNAs was G in the BALB/c and ddY/DAO^– mice whereas it was substituted for C in the ddY/DAO⁺ mice. This base substitution was the cause of the failure of the cleavage of the cDNA of the ddY/DAO⁺ mice.Examination of other strains of inbred mice showed thatd-amino-acid oxidase cDNAs of A/J, AKR, C57BL/6, CD-1, CF#1, ICR, DBA/2, NZB and NZW mice were cleaved withHindIII into two fragments whereas those of C3H/He, CBA/J and NC mice were not. Genomic DNAs extracted from the mice of these 15 strains were digested withHindIII and hybridized withd-amino-acid oxidase cDNA. A 18.2-kb fragment hybridized with the probe in the C3H/He, CBA/J, ddY/DAO⁺ and NC mice whereas two fragments of 12 kb and 6.2 kb hybridized in the other mice. These results are consistent with those of the cDNAs, confirming the loss of theHindIII cleavage site in the C3H/He, CBA/J, ddY/DAO⁺ and NC mice. The Southern hybridization revealed a loss of a differentHindIII cleavage site in the A/J, AKR, C57BL/6, DBA/2, ICR and NZB mice.The substitution at nucleotide-471 should cause a substitution of an amino acid residue. However, this substitution did not affect catalytic activity ofd-amino acid oxidase.     

Genetic Determination of the Developmental Program for Mouse Liver β-GALACTOSIDASE: Involvement of Sites Proximate to and Distant from the Structural Gene

The identification and mode of action of genetic loci that program gene expression during development are important for understanding differentiation in higher organisms. Previous work from this laboratory has identified two patterns for the postnatal development of liver beta-galactosidase among inbred mouse strains: type I, where activity levels remain constant after about 30 days of age, is found in strains DBA/2J, CBA/J, and BALB/cJ, among others; type II, where activity levels increase between 25 and 50 days of age to reach a new adult level, is found in strain C57BL/6J and related strains. It has been shown that the type I vs. type II developmental difference between strains C57BL/6J and DBA/2J is due to variation at a locus, Bgl-t, that maps with the beta-galactosidase complex, [Bgl], on chromosome 9. In the present study, we have confirmed the existence of Bgl-t as a temporal locus within [Bgl] by analysis of both a congenic strain carrying the beta-galactosidase complex of strain CBA/J in the C57BL/6J genetic background and a cross of strains CBA/J and C57BL/6J. The existence of additional temporal loci for beta-galactosidase that segregate independently of the structural gene and participate in determination of the type I vs. type II difference was revealed by analysis of: (1) a congenic strain containing the beta-galactosidase complex of strain BALB/cJ in the C57BL/10Sn background; (2) recombinant inbred lines derived from progenitor strains C57BL/6ByJ and BALB/cByJ; and (3) a genetic cross between strains C57BL/6ByJ and BALB/cByJ. Thus, for these pairs of strains, the type I vs. type II developmental difference is due to variation at a temporal locus (or loci) unlinked to the enzyme structural gene, and not at Bgl-t. These facts, together with information gathered from an examination of the distribution of beta-galactosidase phenotypes among over 100 inbred strains (Breen, Lusis and Paigen 1977), have led us to conclude that the postnatal developmental pattern for liver beta-galactosidase is determined by a set of interacting temporal genes. One of these, Bgl-t, is located within [Bgl], and one or more are separable from [Bgl] by recombination. A possible mode of interaction among the temporal and instructural loci is suggested.     

Genetic regulation of glucose 6-phosphate dehydrogenase activity in the inbred mouse

The erythrocyte glucose 6-phosphate dehydrogenase activity characteristic of each of 16 inbred mouse strains falls into one of three distinct classes. Strains C57L/J and C57BR/cdJ represent the low activity class: strains A/J and A/HeJ represent the high activity class; other strains have intermediate activities. There is no evidence that structural variation is responsible for the variation in G6PD activity, since partially purified enzyme from each class has the same thermal stability, pH-activity profile, Michaelis constants for G6P and NADP, electrophoretic mobility, and activity using 2-deoxy d-glucose 6-phosphate as substrate. The activities of 6-phosphogluconate dehydrogenase and glucose phosphate isomerase do not differ in erythrocytes of the three G6PD activity classes. Young red cells have higher G6PD activities than old red cells and there is evidence that the intracellular stability of the enzyme is reduced in red cells of strain C57L/J. G6PD activities in kidney and skeletal and cardiac muscle from animals with low red cell G6PD are slightly lower than the activities in kidney and muscle from animals with high red cell G6PD activity. The quantitative differences in red cell G6PD activity are not regulated by X-linked genes, but by alleles at two or more autosomal loci. A simple genetic model is proposed in which alleles at two unlinked, autosomal loci, called Gdr-1 and Gdr-2 regulate G6PD activity in the mouse erythrocyte.     

Schistosoma japonicum: Infection characteristics in mice of various strains and a difference in the response to eggs

Female mice of 12 inbred strains were exposed to 20–25 cercariae of Schistosoma japonicum and infection status determined at day 40 by counting numbers of adult worms, eggs in faeces and eggs in a segment of liver. Most mouse strains appeared to be ‘permissive’ hosts although at least one strain (129/J) was shown to be relatively resistant in terms of day 40 adult worm numbers. In a radioisotopic lung assay for sensitivity to eggs, and developed as a rapid means of assessing granuloma formation, CBA/H mice were shown to differ from C57BL/6 mice in being non-responders. Histological examination of lungs of sensitized CBA/H and C57BL/6 mice injected intravenously with eggs established that granuloma formation was much more intense in C57BL/6 than CBA/H mice. Preliminary indications are that infected CBA/H mice are also low anti egg circumoval precipitin (COP) responders. Analysis of immune responses to isolated egg antigens in these two strains, and identification of the antigens of eggs to which such responses are directed in C57BL/6 mice, should provide insights into immunological disease processes (such as granulomatous inflammation) in this model system of japonicum schistosomiasis.     

Moused-amino-acid oxidase gene: Restriction fragment length polymorphism among mouse strains

Summary Genomic DNA was extracted from mice of 15 strains (A/J, AKR, BALB/c, C3H/He, C57BL/6, CBA/J, CD-1, CF#1, DBA/2, ddY/DAO⁺, ddY/DAO^–, ICR, NC, NZB and NZW) for the examination of the difference in the structure of thed-amino-acid oxidase gene among the mouse strains. The DNAs were digested with restriction endonucleases and analyzed by Southern hybridization usingd-amino-acid oxidase cDNA as a probe. The 15 strains showed the same hybridization patterns in theEcoRV,BamHI orBglII digestion. In theEcoRI digestion, the DBA/2 strain showed a different hybridization pattern from the other 14 strains. In thePvuII andXbaI digestion, C3H/He, CBA/J, ddY/DAO⁺ and NC strains were different from the other 11 strains. In thePstI andHindIII digestion, restriction fragment length polymorphisms were observed, and the 15 strains were classified into four groups according to their hybridization patterns. These results indicate that the 15 strains of mice carry a structurally similard-amino-acid oxidase gene, but there is a variation in its inside sequence among the groups of the strains.     

Control of liver tyrosine aminotransferase expression: Enzyme regulatory studies on inbred strains and mutant mice

Studies on the genetic mechanisms in control of mouse liver tyrosine aminotransferase expression were of three general types: (1) studies on strain variance in endogenous enzyme activity and of various factors affecting the basal enzyme level, (2) purification of the enzyme and studies of its properties, and (3) studies of strain variance in enzyme regulation dealing primarily with glucocorticoid induction and with the starvation-induced enzyme adaptation. Tyrosine aminotransferase (l-tyrosine: 2-oxoglutarate aminotransferase, E.C. 2.6.1.5) was purified 400 to 600-fold from livers of C57BL/6J and DBA/2J inbred mice. Several of the properties of the mouse liver enzyme were similar to those known for the rat liver enzyme although the apparent K _m (l-tyrosine) was lower, calculated at 6.25×10^–4 M. Disc gel electrophoresis of the enzyme from 105,000 g supernatant fluid after induction by hydrocortisone indicated three bands of enzyme activity with strain variance in electrophoretic mobility between the C57BL/6J and DBA/2J mice. The administration of glucose to fasting C57BL/6J mice repressed the starvation-induced increase in enzyme activity, but did not prevent the hydrocortisone induction of enzyme activity. DEAE-cellulose chromatography of purified enzyme from fasting DBA/2J and C57BL/6J mice which had been labeled in vivo with C ¹⁴ -l-leucine revealed strain differences in the elution patterns for both enzyme activity and radioactivity. Two peaks of enzyme activity were detected in the enzyme preparations from fasting mice. The marked strain variance in the enzyme activity and the quantity of radioactivity associated with the first enzyme peak may indicate differential rates of protein turnover for different isozymic forms of tyrosine aminotransferase. Flumethasone, a potent difluoro synthetic glucocorticoid, was used in studies on the hormonal regulation of tyrosine aminotransferase in obese mutant mice of the C57BL/6J-ob strain. The obese mice are relatively insensitive to the action of adrenal glucocorticoids to cause liver enzyme induction.This paper was presented at a symposium entitled Genetic Control of Mammalian Metabolism held at The Jackson Laboratory, Bar Harbor, Maine, June 30–July 2, 1969. The symposium was supported in part by an allocation from NIH General Research Support Grant FR 05545 from the Division of Research Resources to The Jackson Laboratory.This investigation was supported in part by an allocation from the NIH General Research Support Grant FR 05545 from the Division of Research Resources to The Jackson Laboratory and in part by Institutional Grant IN-19 from the American Cancer Society to The Jackson Laboratory.     

Rates of sterol synthesis and hydroxymethylglutaryl coenzyme a reductase levels,and the effects of cholest-4-en-3-one on these parameters,in the livers of inbred strains of mice

Hereditary factors in inbred mouse strains affected the rate of sterol synthesis from acetate and the level of hydroxymethylglutaryl coenzyme A reductase in liver in two ways. During the forenoon, rates of sterol synthesis and levels of HMG-CoA reductase activity were two- to five-fold higher in C57L/J and DBA/2J mice than in mice of strains A/HeJ or SWR/J. Due to an apparent difference in the circadian cycle of the two strains, these differences between C57BL/6J and A/HeJ strains were not as great at 4:30 pm, and in some cases the relative order of the values was reversed at this time. Low doses of dietary cholest-4-en-3-one inhibited sterol synthesis and HMG-CoA reductase in livers of all strains tested, whereas high doses or prolonged feeding of the steroid caused a relatively rapid elevation of both sterol synthesis and enzyme activity to above normal levels in several mouse strains including C57L/J. Sterol synthesis and enzyme activity in strain A/HeJ mice were depressed by dietary cholest-4-en-3-one under all conditions tested except when the steroid was fed at a low level for a prolonged period. LAF₁ offspring of the cross C57L/J×A/HeJ responded to dietary cholest-4-en-3-one as did the A/HeJ parental strain. Analysis of the effects of cholest-4-en-3-one upon sterol synthesis in backcross offspring of the mating LAF₁/J×C57L/J did not permit precise estimation of the number of genes that determine the difference in response to the dietary steroid but did suggest that the number may be relatively small.This paper was presented at a symposium entitled Genetic Control of Mammalian Metabolism held at The Jackson Laboratory, Bar Harbor, Maine, June 30–July 2, 1969. The symposium was supported in part by an allocation from NIH General Research Support Grant FR 05545 from the Division of Research Resources to The Jackson Laboratory.Supported in part by NIH Research Grant CA 02758 and NIH Training Grant Tol CA 05013, both from the National Cancer Institute. Some of this work was presented by R.M.P. in partial fulfillment of the requirement for a M.S. degree.     

Strain‐dependent variations in visceral sensitivity: relationship to stress,anxiety and spinal glutamate transporter expression

Responses to painful stimuli differ between populations, ethnic groups, sexes and even among individuals of a family. However, data regarding visceral pain are still lacking. Thus, we investigated differences in visceral nociception across inbred and outbred mouse strains using colorectal distension. Anxiety and depression‐like behaviour were assessed using the open field and forced swim test as well as the corticosterone stress response. Possible mechanistic targets [excitatory amino acid transporter (EAAT‐1), brain‐derived neurotrophic factor (BDNF) and 5HT1A receptor] were also assessed using quantitative real‐time polymerase chain reaction. Adult, male, inbred and outbred mouse strains were used in all assays (inbred strains; CBA/J Hsd, C3H/HeNHsd, BALB/c OlaHsd, C57 BL/6JOlaHsd, DBA/2J RccHsd, CAST/EiJ, SM/J, A/J OlaHsd, 129P2/OlaHsd, FVB/NHan Hsd and outbred strains: Swiss Webster, CD‐1). mRNA expression levels of EAAT‐1, BDNF and 5HT1A receptor (HTR1A) were quantified in the lumbosacral spinal cord, amygdala and hippocampus. A significant effect of strain was found in visceral sensitivity, anxiety and depressive‐like behaviours. Strain differences were also seen in both baseline and stress‐induced corticosterone levels. CBA/J mice consistently exhibited heightened visceral sensitivity, anxiety behaviour and depression‐like behaviour which were associated with decreased spinal EAAT‐1 and hippocampal BDNF and HTR1A. Our results show the CBA/J mouse strain as a novel mouse model to unravel the complex mechanisms of brain–gut axis disorders such as irritable bowel syndrome, in particular the underlying mechanisms of visceral hypersensitivity, for which there is great need. Furthermore, this study highlights the importance of genotype and the consequences for future development of transgenic strains in pain research.     

Differential DNA-repair activity in prespermiogenic cells of various mouse strains

The present report demonstrates differential DNA-repair activity among 14 strains of immature (20 ± 2 days old) male mice (inbred strains: C57BL/6J, RF/J, Nude homo/nu, RIII/2J, Pl/J, AKR/J, Nude hetro/nude, C3H/HeJ, SWR/J, SM/J, ST/J, LP/J, BALB/cJ and random-bred strain: CD-1). The prespermiogenic cells were isolated and enriched by collagenase-trypsin digestion of seminiferous tubules and subsequent 3% albumin-gradient centrifugation. Enriched prespermiogenic cells demonstrated a viabiilty greater than 95% by trypan blue exclusion criteria. For in vitro unscheduled DNA synthesis (UDS) determination, prespermiogenic cells (10⁶ cells/ml) were incubated with methyl methanesulfonate (0.4 mM) in the presence of 20 mM hydroxyurea (HU). At 20 mM HU concentration, 90% of S-phase DNA activity in prespermiogenic cells was inhibited and thus, the net UDS activity following MMS exposure was readily determined. MMS-induced UDS activity in the CD-1 mouse strain was both linear up to 4 h of incubation and dose-dependent at 4 h incubation. The apparent K_m for MMS-induced UDS activity in prespermiogenic cells was approx. 1.8 × 10^?4 M. Of the 14 mice strains tested, C57BL/6J and RF/J exhibited the highest DNA-repair activity, while BALB/cJ, LP/J, and ST/J showed the lowest. A maximal difference in UDS activity fo 3.5-fold was observed between C57BL/6J and BALB/cJ. Furthermore, a 2.5-fold difference was also noted between RF/J and LP/J mouse strains. Thus, wide variations in DNA-repair activity among 14 mouse strans were clearly demonstrated. Whether genetically select mouse strains with the lowest DNA-repair activity should have greater sensitivity toward environmental mutagens needs to be tested.     

Radiation-induced pulmonary endothelial dysfunction and hydroxyproline accumulation in four strains of mice

C57BL mice exposed to 14 Gy of whole-thorax irradiation develop significant histologic lung fibrosis within 52 weeks, whereas CBA and C3H mice do not exhibit substantial fibrosis during this time. The purpose of the present study was to determine whether this strain-dependent difference in radiation histopathology is associated with genetic differences in pulmonary endothelial metabolic activity or in endothelial radioresponsiveness. C57BL/6J, C57BL/10J, CBA/J, and C3H/HeJ mice were sacrificed 12 weeks after exposure to 0 or 14 Gy of 300-kV X rays to the whole thorax. Lung angiotensin converting enzyme (ACE) activity and plasminogen activator (PLA) activity were measured as indices of pulmonary endothelial function; and lung hydroxyproline (HP) content served as an index of pulmonary fibrosis. Lung ACE and PLA activities in sham-irradiated C57BL/6J and CB57BL/10J mice were only half as high as those in sham-irradiated CBA/J and C3H/HeJ mice. Exposure to 14 Gy of X rays produced a slight but nonsignificant reduction in lung ACE and PLA activity in the C57BL strains, and a significant reduction in the CBA/J and C3H/HeJ mice. Even after 14 Gy, however, lung ACE and PLA activities in CBA/J and C3H/HeJ mice were higher than those in sham-irradiated C57BL/6J and C57BL/10J mice. Lung HP content in all four strains increased significantly after irradiation, but this increase was accompanied by an increase in lung wet weight. As a result, HP concentration (per milligram wet weight) remained constant or increased slightly in both C57BL strains and actually decreased in the CBA/J and C3H/HeJ mice. These data demonstrate significant genetic differences in both intrinsic pulmonary endothelial enzyme activity and endothelial radioresponsiveness among the four strains of mice. Specifically, strains prone to radiation-induced pulmonary fibrosis (C57BL/6J, C57BL/10J) exhibit only half as much lung ACE and PLA activity as do strains resistant to fibrosis (CBA and C3H).     

Exploratory activity of mice of different genetic strains after olfaction disruption by 3-methylindole (skatole)

The behavior of mice of two inbred strains (C57BL/6J and CBA) and their F1 hybrids was evaluated in the open field test after intraperitoneal administration of 3-methylindole (skatole) disrupting epithelium of the main olfactory system. High motor and exploratory activities and emotional sensitivity was observed in intact C57BL/6J mice compared to CBA mice and their hybrids. Anosmia induced by intraperitoneal administration of skatole changed the behavior of C57BL/6J and CBA mice. The direction of the observed changes in the orientation and exploratory behavior of anosmic animals was different. Anosmia decreased motor and exploratory activities in C57BL/6J mice and increase them in CBA mice. Intact hybrid mice demonstrated the predominance of the CBA genotype in the orientation and exploratory activity in the test used. Anosmia in hybrid animals had no significant effect on the orientation and exploratory behavior.     

A gene apparently determining the extent of sialylation of lysosomal α-mannosidase in mouse liver

Organ-specific electrophoretic heterogeneity of lysosomal -mannosidase has been observed within individual strains of inbred mice. Polymorphism between C57BL/6J and CBA/J for liver lysosomal -mannosidase is determined by a single genetic locus on chromosome 5 and appears to be the result of differences in sialylation of the lysosomal enzyme. Two different patterns of expression of development of the liver electrophoretic forms have been observed.Supported in part by Grant GM-19521 from the U.S. Public Health Service. One of the authors (M.D.) was supported in part from USPHS Grant TAO-CA05016.     

Allotypes of mouse complement component C6 in inbred strains and some wild populations

This collaborative work was undertaken to resolve discrepancies in reports of the number of forms of complement component C6 present in the circulation of mice from various inbred strains. Plasma C6 was analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate and by isoelectric focusing (IEF), and C6 band patterns were developed by electroblotting and immunoprobing. Results of C6 allotyping of mice from 36 strains confirmed that while 20 strains (prototype strain BALB/c) possessed only one relative mass (M _r) form which typed C6A1 on IEF, the other 16 strains all possessed more than one C6 M _r form. Moreover, IEF analysis demonstrated additional polymorphic differences; among these 16 strains, 11 typed C6A l B l like the prototype strain CBA, the AKR and RF/J strains typed C6A2B2, and the Japanese MOM strain as well as the C57BR/cdJ and C57L/J strains possessed two forms with IEF mobilities intermediate between C6A1B1 and C6A2B2. These will now be referred to as C6A3B3. Thus, a total of four different mouse C6 haplotypes have been identified.Testing C6 allotypes in a limited number of wild mice revealed that haplotypes found in inbred strains of Western or Eastern origin tend to reflect haplotypes of the wild mice from Europe or Japan, respectively.     

Purification and characterization of two allelic forms of l-glycerol 3-phosphate dehydrogenase from inbred strains of mice

l-Glycerol 3-phosphate dehydrogenase (E.C. 1.1.1.8) was purified from the muscle of BALB/cJ and C57BL/6J mice. The half-lives of the enzyme at 50 C were 6 and 33 min, respectively, for the BALB/cJ and C57BL/6J strains. Enzyme preparations from the two strains of mice were compared with respect to the following properties and found to be essentially indistinguishable: K _m values for dihydroxyacetone phosphate, NADH, l--glycerophosphate, and NAD⁺; maximum velocity; competitive inhibition by inorganic phosphate; pH optimum; energy of activation; electrophoretic mobility; molecular weight and subunit molecular weight. From these data, it is concluded that the kinetic properties of the purified enzyme are not the factors responsible for the differences in activity found in crude homogenates of mouse tissues.This work was supported by NIH Research Grant HD 06712 from the National Institute of Child Health and Human Development and by an allocation from NIH General Research Support Grant RR-05545 from the Division of Research Resources to The Jackson Laboratory. The Jackson Laboratory is fully accredited by the American Association for Accreditation of Laboratory Animal Care.     

A comparative study of the susceptibility of inbred strains of mice to infection with Mesocestoides corti

White T. R., Thompson R. C. A. and Penhale W. J. 1982. A comparative study of the susceptibility of inbred strains of mice to infection with Mesocestoides corti. International Journal for Parasitology12: 29–33. The susceptibility of 6 strains of inbred mice to infection with Mesocestoides corti was studied following both intraperitoneal and oral inoculation of tetrathyridia. The greatest degree of resistance was seen in C57BL/6 mice and this resistance was independent of route of inoculation. The proliferation of the parasite in C57BL/6 mice was compared with a more susceptible strain (CBA/H) on 7, 14, 21, 35 and 60 days post-infection. Although both strains harboured significantly different parasite burdens during the initial period following infection, these differences were no longer apparent by day 60.     

Q- and C-Band Chromosome Markers in Inbred Strains of MUS MUSCULUS

Differences in the number of chromosomes with secondary constrictions and in the size of the C-band region on certain chromosomes have been observed among the following inbred strains of Mus musculus: C57BL/10J, C57BR/cdJ, DBA/1J, CBA/J, BALB/cJ, and AKR. These differences are useful as indicators of the location of rRNA genes and as normal chromosome markers. The size of each C-band region appears to remain constant over many generations. Only one probable change in the size of a C-band region was found.     

Quantitative trait locus and haplotype mapping in closely related inbred strains identifies a locus for open field behavior

Quantitative trait locus (QTL) mapping in the mouse typically utilizes inbred strains that exhibit significant genetic and phenotypic diversity. The development of dense SNP panels in a large number of inbred strains has eliminated the need to maximize genetic diversity in QTL studies as plenty of SNP markers are now available for almost any combination of strains. We conducted a QTL mapping experiment using both a backcross (N₂) and an intercross (F₂) between two genetically similar inbred mouse strains: C57BL/6J (B6) and C57L/J (C57). A set of additive QTLs for activity behaviors was identified on Chrs 1, 9, 13, and 15. We also identified additive QTLs for anxiety-related behaviors on Chrs 7, 9, and 16. A QTL on Chr 11 is sex-specific, and we revealed pairwise interactions between QTLs on Chrs 1 and 13 and Chrs 10 and 18. The Chr 9 activity QTL accounts for the largest amount of phenotypic variance and was not present in our recent analysis of a B6 × C58/J (C58) intercross (Bailey et al. in Genes Brain Behav 7:761–769, 2008). To narrow this QTL interval, we used a dense SNP haplotype map with over 7 million real and imputed SNP markers across 74 inbred mouse strains (Szatkiewicz et al. in Mamm Genome 19(3):199–208, 2008). Evaluation of shared and divergent haplotype blocks among B6, C57, and C58 strains narrowed the Chr 9 QTL interval considerably and highlights the utility of QTL mapping in closely related inbred strains.     

Evidence for a possible regulatory gene (Suc-1) controlling sucrase expression in mouse intestine

Assays for sucrase carried out on intestinal sonicates prepared from 18 different strains of mice revealed a threefold variation in specific activity, the values for CBA/Ca mice being significantly less than for any other strain. Further comparison of the CBA/Ca versus the C57BL/6J mouse showed this deficiency, which became established 2–4 weeks after birth, to apply to isomaltase as well as sucrase but not to maltase or trehalase. Backcross experiments indicated that this deficiency in sucrase activity was inherited as a single codominantly expressed genetic factor. The ability of the CBA/Ca mouse to regulate sucrase activity in response to changes in diet was also reduced compared to that of the C57BL/6J mouse. No difference could be detected in the affinity of sucrase for its substrate or in the ability of heat to denature sucrase prepared from CBA/Ca and C57BL/6J mice. It is suggested that part of the regulatory region of the gene coding for sucrase-isomaltase is modified in the CBA/Ca mouse and that this locus should be given the notation Suc-1 for future reference.This work supported by an MRC project grant to M. W. Smith.