Genetic analysis of barrel field size in the first somatosensory area (SI) in inbred and recombinant inbred strains of mice

We measured the combined area of posterior medial barrel subfield (PMBSF) and anterior lateral barrel subfield (ALBSF) areas in four common inbred strains (C3H/HeJ, A /J, C57BL /6J, DBA/2J), B6D2F1, and ten recombinant inbred (RI) strains generated from C57BL/6J and DBA/2J progenitors (BXD) as an initial attempt to examine the genetic influences underlying natural variation in barrel field size in adult mice. These two subfields are associated with the representation of the whisker pad and sinus hairs on the contralateral face. Using cytochrome oxidase labeling to visualize the barrel field, we measured the size of the combined subfields in each mouse strain. We also measured body weight and brain weight in each strain. We report that DBA/2J mice have a larger combined PMBSF/ALBSF area (6.15 +/- 0.10 mm(2), n = 7) than C57BL /6J (5.48 +/- 0.13 mm(2), n = 10), C3H/HeJ (5.37 +/- 0.16 mm(2), n = 10), and A/J mice (5.04 +/- 0.09 mm(2), n = 15), despite the fact that DBA/2J mice have smaller average brain and body sizes. This finding may reflect dissociation between systems that control brain size with those that regulate barrel field area. In addition, BXD strains (average n = 4) and parental strains showed considerable and continuous variation in PMBSF/ALBSF area, suggesting that this trait is polygenic. Furthermore, brain, body, and cortex weights have heritable differences between inbred strains and among BXD strains. PMBSF/ALBSF pattern appears similar among inbred and BXD strains, suggesting that somatosensory patterning reflects a common plan of organization. This data is an important first step in the quantitative genetic analysis of the parcellation of neocortex into diverse cytoarchitectonic zones that vary widely within and between species, and in identifying the genetic factors underlying barrel field size using quantitative trait locus (QTL) analyses.     

Independent genetic loci for sensorimotor gating and attentional performance in BXD recombinant inbred strains

A startle reflex in response to an intense acoustic stimulus is inhibited when a barely detectable pulse precedes the startle stimulus by 30-500 ms. It has been theorized that this phenomenon, named prepulse inhibition (PPI) of a startle response, is an automatic early-stage gating process contributing to the ability to focus attention. Deficits in PPI may therefore contribute to deficits in attentional processing. Both deficits are observed in schizophrenia spectrum disorders. Here, we investigated whether there is overlap in genetic control of PPI and attentional processing phenotypes in the panel of BXD recombinant inbred strains of mice. Using an individually titrated prepulse intensity to handle differences in perceived prepulse intensities among strains, we identified a significant quantitative trait locus (QTL) for PPI at the mid-distal end of chromosome 17. A measure of attentional processing in the five-choice serial reaction time task, response variability, mapped to a different locus on proximal-mid chromosome 16. In addition, the estimated genetic and environmental correlations between PPI and several attentional phenotypes were low and not significant. Taken together, the observation of separate genetic loci for PPI and attention and the absence of genetic and environmental correlations indicate that differences in sensorimotor gating do not contribute to differences in attentional performance. Therefore, it is worth pursuing the causative genes residing in both attention and PPI QTL, as these may contribute to separate molecular pathways implicated in neuropsychiatric diseases, such as schizophrenia.     

The relative affective potency of glycine, L-serine and sucrose as assessed by a brief-access taste test in inbred strains of mice

In general, rodents prefer both sucrose and L-serine relative to water and treat both compounds as possessing a similar taste quality (e.g. 'sweetness') despite that they are believed to bind with different T1R heterodimeric receptors in taste bud cells. We assessed the affective potency of these compounds along with glycine, which is thought to bind with both T1R receptor complexes, using a brief-access taste test in a gustometer. Unconditioned licking responses of two 'taster' strains (C57BL/6J and SWR/J), which display high preference for low concentrations of sucrose, and two 'non-taster' (129P3/J and DBA/2J) strains, which display blunted preference for low concentrations of sucrose, were measured during 5 s trials of varying concentrations of a single compound when mice (n=10/strain/stimulus) were non-deprived and when access to home-cage water was restricted. In non-deprived mice, sucrose generated monotonically increasing concentration-response curves regardless of strain, whereas glycine was only marginally effective at stimulating licking and L-serine produced relatively flat functions. The profile of responsiveness across strains was more complex than expected. For example, when tested with sucrose in the non-deprived condition, the 129P3/J non-taster strain surpassed the responsiveness of taster mice at mid-range to high concentrations. Under water-restricted conditions, these mice also were significantly more responsive to high concentrations of both sucrose and glycine compared with the other strains when stimulus licking was standardized relative to water. Thus, the affective potency of the stimuli tested here seems to be related to the ability of the compounds to bind with the T1R2+3 receptor complex. However, the profile of strain responsiveness to these tastants in the brief-access test does not appear to be simply explained by the sweetener 'taster' status of the strain.     

Variation in nicotine consumption in inbred mice is not linked to orosensory ability

Genetic studies of nicotine addiction in mice have utilizedthe oral self-administration model. However, it is unclear ifstrain differences in nicotine consumption are influenced byvariation in bitter taste sensitivity. We measured both nicotineconsumption and nicotine brief-access licking behavior in severalcommonly used inbred strains of mice that were previously shownto differ in nicotine consumption. A/J (A), C57BL/6J (B6), andDBA/2J (D2) mice were given a 2-bottle choice test with a singleconcentration of nicotine (75 µg/ml; nicotine vs. water).Mice of these strains were also tested with a range of nicotineconcentrations (5–400 µg/ml) using a brief-accesstest, which measures orosensory response and minimizes postingestiveeffects. Although B6 mice consumed more 75-µg/ml nicotinethan A or D2 mice in the 2-bottle test, these strains did notdiffer in level of aversion to nicotine when tested with thebrief-access procedure. Strain differences in orosensory responseto nicotine were not found; yet, differences emerged duringthe 2-bottle tests. This study provides evidence that variationin intake level of nicotine is likely not due to differencesin taste or trigeminal sensitivity but likely due to postingestivefactors.     

A parametric analysis of factors affecting acquisition and extinction of contextual fear in C57BL/6 and DBA/2 mice

Behavioral analyses of genetically modified and inbred strains of mice have revealed neural systems and molecules that are involved in memory formation. Many of these studies have examined memories that form in contextual fear conditioning, in which an organism learns that a particular context signals the occurrence of a footshock. During fear extinction, nonreinforced exposure to the context results in the loss of the conditioned fear response. The study of extinction has been instrumental for behavioral and molecular theories of memory. However, many of the transgenic, knockout, and inbred strains of mice that have been widely studied in memory have behavioral deficits in contextual fear conditioning, which makes the study of extinction in these mice particularly challenging. Here we explore several strategies for studying extinction in C57BL/6 and DBA/2 mice, two strains known to differ in contextual fear conditioning. First, we attempt to equate performance prior to extinction through several extensive conditioning protocols. Second, we examine extinction in subsets of mice matched for initial levels of context conditioning. Third, we examine within-strain effects of variables known to affect extinction. Differences between the strains persisted across extensive conditioning and extinction protocols, but both strains were sensitive to session duration and context manipulations during extinction. We describe the implications of our results for behavioral and neurobiological approaches to extinction, and we examine the general challenges in studying extinction in subjects that differ in learning or performance prior to extinction.     

Differential expression and regulation of myristoylated alanine-rich C kinase substrate (MARCKS) in the hippocampus of C57/BL6J and DBA/2J mice

The myristoylated alanine-rich C kinase substrate (MARCKS) is a major protein kinase C (PKC) substrate in brain that binds the inner surface of the plasma membrane, calmodulin, and cross-links filamentous actin, all in a PKC phosphorylation-reversible manner. MARCKS has been implicated in hippocampal-dependent learning and long-term potentiation (LTP). Previous studies have shown DBA/2 mice to exhibit poor spatial/contextual learning, impaired hippocampal LTP, and hippocampal mossy fiber hypoplasia, as well as reduced hippocampal PKC activity and expression relative to C57BL/6 mice. In the present study, we assessed the expression (mRNA and protein) and subcellular distribution (membrane and cytolsol) of MARCKS in the hippocampus and frontal cortex of C57BL/6 and DBA/2 mice using quantitative western blotting. In the hippocampus, total MARCKS mRNA and protein levels in C57BL/6J mice were significantly lower ( approximately 45%) compared with DBA/2J mice, and MARCKS protein was observed predominantly in the cytosolic fraction. MARCKS expression in frontal cortex did not differ significantly between strains. To examine the dynamic regulation of MARCKS subcellular distribution, mice from each strain were subjected to 60 min restraint stress and MARCKS subcellular distribution was determined 24 h later. Restraint stress resulted in a significant reduction in membrane MARCKS expression in C57BL/6J hippocampus but not in the DBA/2J hippocampus despite similar stress-induced increases in serum corticosterone. Restraint stress did not affect cytosolic or total MARCKS levels in either strain. Similarly, restraint stress (30 min) in rats also induced a significant reduction in membrane MARCKS, but not total or cytosolic MARCKS, in the hippocampus but not in frontal cortex. In rats, chronic lithium treatment prior to stress exposure reduced hippocampal MARCKS expression but did not affect the stress-induced reduction in membrane MARCKS. Collectively these data demonstrate higher resting levels of MARCKS in the hippocampus of DBA/2J mice compared to C57BL/6J mice, and that acute stress leads to a long-term reduction in membrane MARCKS expression in C57BL/6J mice and rats but not in DBA/2J mice. These strain differences in hippocampal MARCKS expression and subcellular translocation following stress may contribute to the differences in behaviors requiring hippocampal plasticity observed between these strains.     

Acute locomotor responses to cocaine in adolescents vs. adults from four divergent inbred mouse strains

Growing evidence suggests that adolescent mice display differential sensitivity to the acute locomotor activating effects of cocaine as compared to adults, but the direction of the difference varies across studies and the reasons are not clear. Few studies have directly examined genetic contributions to age differences in locomotor stimulation from cocaine. The goal of this study was to determine the extent to which reduced stimulation in C57BL/6J adolescents as compared to adults generalizes to other strains. Therefore, we examined male and female mice from four genetically divergent inbred stains (BALB/cByJ, C57BL/6J, DBA/2J and FVB/NJ) at two ages, postnatal day 30 and postnatal day 65. Mice received either saline or cocaine (15 or 30 mg/kg), and then immediately were placed back into their home cages. Locomotor activity was recorded continuously in the home cage by video tracking. Adolescents displayed reduced stimulation as compared to adults for C57BL/6J, BALB/cByJ and female FVB/NJ mice. No age differences were observed for DBA/2J or male FVB/NJ. No main effects of sex were observed. Strain differences in pharmacokinetics, neural development or physiology could contribute to the observed differences between ages across strains. Future comparative studies could discover biological differences between strains that explain age differences in cocaine sensitivity.     

Genetic differentiation within the inbred C57BL/6J mouse strain

The C57BL/6J (B6) inbred mouse strain is commonly used in biomedical researches. However, some unexpected inconsistency was reported compared with previous studies, and in most cases, it can be attributed to environmental, epigenetic or stochastic differences. The goal of this study was to investigate the genetic stability of the B6 strain maintained in different breeders. B6 mice purchased from five Chinese commercial breeders were examined, and mitochondrial D-loop sequence and 18 microsatellite loci were genotyped. There is no difference in the D-loop sequences, but variations exist in the nucleic microsatellite markers. Combining the data from MGI_4.01, a significant divergence is observed among those mice. The present study indicates that different B6 mice share the common maternal lineage and are still inbred in each breeder, but subline divergence occurs.     

Variations in the response of five strains of mice to Leishmania mexicana.

Five strains of mice were studied in their ability to support Leishmania mexicana infection. Four strains, AKR, C57BL/6, DBA/2 and NMRI, were relatively resistant to cutaneous leishmaniasis. These strains developed delayed type hypersensitivity responses to leishmanial antigens and produced agglutinating antibodies. On the other hand Balb/c mice, highly susceptible to infection, failed to develop delayed type hypersensitivity responses and showed an impaired production of antibodies. Hybrids produced by mating C57BL/6 males and Balb/c females were no more susceptible than C57BL/6 mice, suggesting that resistance is inherited as a dominant character.     

Stimulus processing of glycine is dissociable from that of sucrose and glucose based on behaviorally measured taste signal detection in Sac 'taster' and 'non-taster' mice

Mouse strains have been divided into 'tasters' and 'non-tasters' based on their relatively high and low preference, respectively, for low concentrations of sucrose and saccharin. These phenotypic differences appear to be due to a polymorphism in the gene at the Sac locus encoding for the T1R3 taste receptor selectively affecting the functionality of the T1R2+3 heterodimer. To psychophysically examine whether these phenotypes are due to sensory sensitivity as opposed to hedonic responsiveness, we measured taste signal detection of sucrose, glucose, and glycine by Sac taster (C57BL/6J and SWR/J) and non-taster (129P3/J and DBA/2J) strains in an operant conditioning paradigm using a gustometer. The taster mice had lower detection thresholds for sucrose and glucose compared with the non-taster mice. The detection thresholds corresponded well with reported responsiveness to low concentrations of these sugars in two-bottle intake tests suggesting that the Sac taster phenotype has a sensory basis and is not simply a matter of strain differences in the hedonic evaluation of weak intensities of the stimuli. Taster status did not entirely account for the strain differences in detection thresholds for glycine, a 'sweet' tasting amino acid. Collapsed across strains, detection thresholds for sucrose and glucose were highly correlated with each other (r = 0.81), but only modestly correlated with those for glycine (r < or = 0.43). This suggests that stimulus processing of glycine in the perithreshold intensity domain can be dissociated from that of sucrose and glucose. The mechanism underlying this difference may be related to the ability of glycine to bind with the T1R1+3 heterodimer.     

Genetic basis for the psychostimulant effects of nicotine: a quantitative trait locus analysis in AcB/BcA recombinant congenic mice

Genetic differences in sensitivity to nicotine have been reported in both animals and humans. The present study utilized a novel methodology to map genes involved in regulating both the psychostimulant and depressant effects of nicotine in the AcB/BcA recombinant congenic strains (RCS) of mice. Locomotor activity was measured in a computerized open-field apparatus following subcutaneous administration of saline (days 1 and 2) or nicotine on day 3. The phenotypic measures obtained from this experimental design included total basal locomotor activity, as well as total nicotine activity, nicotine difference scores, nicotine percent change and nicotine regression residual scores. The results indicated that the C57BL/6J (B6) were insensitive to nicotine over the entire dose-response curve (0.1, 0.2, 0.4 and 0.8 mg/kg). However, the 0.8-mg/kg dose of nicotine produced a significant decrease in the locomotor activity in the A/J strain and a wide and continuous range of both locomotor excitation and depression among the AcB/BcA RCS. Single-locus association analysis in the AcB RCS identified quantitative trait loci (QTL) for the psychostimulant effects of nicotine on chromosomes 11, 12, 13, 14 and 17 and one QTL for nicotine-induced depression on chromosome 11. In the BcA RCS, nicotine-induced locomotor activation was associated with seven putative regions on chromosomes 2, 7, 8, 13, 14, 16 and 17. There were no overlapping QTL and no genetic correlations between saline- and nicotine-related phenotypes in the AcB/BcA RCS. A number of putative candidate genes were in proximity to regions identified with nicotine sensitivity, including the alpha2 subunit of the nicotinic acetylcholine receptor and the dopamine D3 receptor.     

Strain variation in response to lung ischemia: role of MMP-12

Background

Systemic neovascularization of the lung during chronic ischemia has been observed in all mammals studied. However, the proteins that orchestrate the complex interaction of new vessel growth and tunneling through lung tissue matrix have not been described. Although previous work has demonstrated the CXC chemokines are essential growth factors in the process of angiogenesis in mice and rats, key matrix proteins have not been identified.

Methods

Since the degradation of chemokines has been shown to be dependent on metalloproteinases (MMP), we first surveyed gene expression patterns (real time RT-PCR) of several lung matrix proteins in DBA/J (D2) mice and C57Bl/6 (B6) mice, strains known to have divergent parenchymal responses in other lung disease models. We studied changes in the time course of MMP-12 activity in D2 and B6 mice. Functional angiogenesis was determined 14 days after the onset of complete left lung ischemia induced by left pulmonary artery ligation (LPAL), using fluorescent microspheres.

Results

Our results confirmed higher levels of MMP-12 gene expression in D2 mice relative to B6, which corresponded to a phenotype of minimal systemic angiogenesis in D2 mice and more robust angiogenesis in B6 mice (p < 0.01). MMP-12 activity decreased over the course of 14 days in B6 mice whereas it increased in D2 mice (p < 0.05). MMP-12 was associated largely with cells expressing the macrophage marker F4/80. Genetic deficiency of MMP-12 resulted in significantly enhanced neovascularization (p < 0.01 from B6).

Conclusion

Taken together, our results suggest macrophage-derived MMP-12 contributes to angiostasis in the ischemic lung.     

Susceptibility to re-infection in C57BL/6 mice with recombinant strains of Toxoplasma gondii

This work reports results of re-infection of BALB/c and C57BL/6 mice with different recombinant strains of Toxoplasma gondii. Mice were prime-infected with the non-virulent D8 strain and challenged with virulent strains. PCR–RFLP of cS10-A6 genetic marker of T. gondii demonstrated that BALB/c mice were re-infected with the EGS strain, while C57BL/6 mice were re-infected with the EGS and CH3 strains. Levels of IFN-γ and IL-10 after D8 prime-infection were lower in C57BL/6 than in BALB/c mice. Brain inflammation after D8 prime-infection was more intense in C57BL/6 than in BALB/c mice. It was shown that re-infection depends on mice lineage and genotype of the strain used in the challenge.     

Genetic architecture of the mouse hippocampus: identification of gene loci with selective regional effects

We recently mapped two quantitative trait loci that have widespread effects on hippocampal architecture in mouse: Hipp1a and Hipp5a. We also noted remarkable strain differences in the relative sizes of different hippocampal regions. Estimated heritable variation for these differences was 42% in hippocampus proper, 40% in dentate gyrus, 31% in granule cell layer and 18% in pyramidal cell layer. Region size varied at least 50% from largest to smallest measurement. Here we have utilized these differences to identify loci with effects on the dentate gyrus, granule cell layer, hippocampus proper and pyramidal cell layer. Our sample consists of C57BL/6J and DBA/2J and 32 BXD recombinant inbred strains. Volumetric data were corrected for shrinkage and for differences in brain weight. We identified significant loci on chromosomes (Chr) 6, 13 and 15, and a significant interaction locus on proximal Chr 11. A suggestive distal Chr 1 locus overlaps with Hipp1a. HipV13a (Chr 13, 42-78Mb) has an additive effect of 0.56 mm3 (12.1%) on dentate gyrus volume, while GrV6a (Chr 6, 29-65 Mb) has additive effects of 0.14 mm3 (16.0%) on the volume of the granule cell layer. HipV13a also interacts with DGVi11a, a locus on proximal Chr 11 that operates exclusively through its epistatic effect on HipV13a and has no independent main effect HipV15a (Chr 15, 0-51 Mb) has an additive effect of 1.76 mm3 (9.0%) on the volume of the hippocampus proper. We used WebOTL, a recently described web-based tool, to examine genetic correlation of gene expression with hippocampal volume. We identified a number of genes that map within the OTL intervals and have highly correlated expression patterns. Using WebQTL's extensive database of published BXD phenotypes, we also detected a strong and potentially biologically meaningful correlation between hippocampal volume and the acoustic startle response.     

The mouse antibody heavy chain repertoire is germline-focused and highly variable between inbred strains

The human and mouse antibody repertoires are formed by identical processes, but like all small animals, mice only have sufficient lymphocytes to express a small part of the potential antibody repertoire. In this study, we determined how the heavy chain repertoires of two mouse strains are generated. Analysis of IgM- and IgG-associated VDJ rearrangements generated by high-throughput sequencing confirmed the presence of 99 functional immunoglobulin heavy chain variable (IGHV) genes in the C57BL/6 genome, and inferred the presence of 164 IGHV genes in the BALB/c genome. Remarkably, only five IGHV sequences were common to both strains. Compared with humans, little N nucleotide addition was seen in the junctions of mouse VDJ genes. Germline human IgG-associated IGHV genes are rare, but many murine IgG-associated IGHV genes were unmutated. Together these results suggest that the expressed mouse repertoire is more germline-focused than the human repertoire. The apparently divergent germline repertoires of the mouse strains are discussed with reference to reports that inbred mouse strains carry blocks of genes derived from each of the three subspecies of the house mouse. We hypothesize that the germline genes of BALB/c and C57BL/6 mice may originally have evolved to generate distinct germline-focused antibody repertoires in the different mouse subspecies.     

Developmental Changes in Brain Glucose, Glycogen, Phosphocreatine, and ATP Levels in DBA/2J and C57BL/6J Mice, and Audiogenic Seizures

Abstract. Brains of rodents are primarily dependent on ketone bodies as a source of hydrogen for NADH and of acetyl-CoA during the perinatal period characterized by suckling. A mouse dam begins to wean her pups at about 14 days of age (DOA), the same age at which the brain reaches near-adult size and begins to shift to dependence on carbohydrate-derived sources of acetyl-CoA for normal function. Also at this time, the ear canals open, and mice of some strains become susceptible to audiogenic seizures (AGS). There may be a genetically determined derangement in the orderly transition from one source of brain energy to the other in AGS-prone mice, with a concomitant brief (days) reduction in the in situ energy reserve during the transition. In mice with a decreased energy reserve, a large energy expenditure within a short period of time (s), such as that induced by a substantial acoustic stimulus to newly opened acoustic pathways, might briefly lead to CNS disorganization before body energy repletion processes may occur, resulting in the onset of an AGS. Since glucose, glycogen, ATP, and phosphocreatine provide the bulk of the brain energy reserve, a developmental study was performed to measure the concentrations of these metabolites in brain tissues of DBA/2J mice (genetically/developmentally susceptible to AGS: onset at 12–14 DOA, peak at 18–21 DOA, rapid decline until 30 DOA, essentially lost by 42 DOA) and in C57BL/6J mice (not developmentally susceptible to AGS). Samples of frontal, temporal, cerebellar, and diencephalic regions were taken from mice 0–44 DOA and assayed. With the exception of higher glycogen levels in both DBA and C57 mice in cerebellar and diencephalic samples 0–16 DOA, no regional differences were found. A decrease in glycogen in all regions was observed in DBA mice 16–30 DOA, which was the inverse of susceptibility to AGS in these mice. This dip was not found in C57 mice. ATP levels were elevated in DBA mice 14–18 DOA, and glucose levels were decreased in DBA mice 24–40 DOA. These data lend support to the hypothesis that lowered brain energy reserves, or lowered access to brain reserves, underlies susceptibility to AGS.     

Comparative gene expression analysis of the engulfment and cell motility (ELMO) protein family in the mouse brain

Engulfment and cell motility (ELMO) proteins bind to Dock180, a guanine nucleotide exchange factor (GEF) of the Rac family, and regulate GEF activity. The resultant ELMO/Dock180/Rac module regulates cytoskeletal reorganization responsible for the engulfment of apoptotic cells, cell migration, and neurite extension. The expression and function of Elmo family proteins in the nervous system, however, are not yet fully understood. Here, we characterize the comparative gene expression profiles of three Elmo family members (Elmo1, Elmo2, and Elmo3) in the brain of C57BL/6J mice, a widely used inbred strain, together with reeler mutant mice to understand gene expression in normal laminated brain areas compared with abnormal areas. Although all three Elmo genes showed widespread mRNA expression over various mouse tissues tested, Elmo1 and Elmo2 were the major types expressed in the brain, and three Elmo genes were up-regulated between the first postnatal week (infant stage) and the third postnatal week (juvenile, weaning stage). In addition, the mRNAs of Elmo genes showed distinct distribution patterns in various brain areas and cell-types; such as neurons including inhibitory interneurons as well as some non-neuronal cells. In the cerebral cortex, the three Elmo genes were widely expressed over many cortical regions, but the predominant areas of Elmo1 and Elmo2 expression tended to be distributed unevenly in the deep (a lower part of the VI) and superficial (II/III) layers, respectively, which also changed depending on the cortical areas and postnatal stages. In the dentate gyrus of the hippocampus, Elmo2 was expressed in dentate granule cells more in the mature stage rather than the immature-differentiating stage. In the thalamus, Elmo1 but not the other members was highly expressed in many nuclei. In the medial habenula, Elmo2 and Elmo3 were expressed at intermediate levels. In the cerebellar cortex, Elmo1 and Elmo2 were expressed in differentiating-mature granule cells and mature granule cells, respectively. In the Purkinje cell layer, Elmo1 and Elmo2 were expressed in Purkinje cells and Bergmann glia, respectively. Disturbed cellular distributions and laminar structures caused by the reeler mutation did not severely change expression in these cell types despite the disturbed cellular distributions and laminar structures, including those of the cerebrum, hippocampus, and cerebellum. Taken together, these results suggested that these three Elmo family members share their functional roles in various brain regions during prenatal-postnatal development.     

Genetic analysis of tongue size and taste papillae number and size in recombinant inbred strains of mice

Quantitative trait loci (QTLs) analysis has been used to examine natural variation of phenotypes in the mouse somatosensory cortex, hippocampus, cerebellum, and amygdala. QTL analysis has also been utilized to map and identify genes underlying anatomical features such as muscle, organ, and body weights. However, this methodology has not been previously applied to identification of anatomical structures related to gustatory phenotypes. In this study, we used QTL analysis to map and characterize genes underlying tongue size, papillae number, and papillae area. In a set of 43 BXD recombinant inbred (RI) mice (n = 111) and 2 parental strains (C57BL/6J and DBA/2J; n = 7), we measured tongue length, width, and weight. In a subset of 23 BXD RI mice and the parental mice, we measured filiform and fungiform papillae number and fungiform papillae area. Using QTL linkage analysis (through WebQTL), we detected 2 significant and noninteracting QTLs influencing tongue length on chromosomes 5 and 7. We also found a significant QTL on chromosome 19 underlying fungiform papillae area and a suggestive QTL on chromosome 2 linked to fungiform papillae number. From these QTLs, we identified a number of candidate genes within the QTL intervals that include SRY-box containing gene, nebulin-related anchoring protein, and actin-binding LIM protein 1. This study is an important first step in identifying genetic factors underlying tongue size, papillae size, and papillae number using QTL analysis.