Spectral Karyotyping in Mice

Spectral karyotyping (SKY) of mouse meioticchromosomes

Henry H.Q. Heng, Guo Liu, Wei Lu, Steve Bremer, Christine J. Ye, Mark Hughes,and Peter Moens

Abstract: The spectral karyotyping procedure of in situ hybridization with chromosome-specific probes assigns aunique colour code to each of the 21 mouse mitotic chromosomes. We have adapted this procedure to meiotic prophasechromosomes, and the results show that each of the pachytene or metaphase I bivalents can be identified. This tech-nique has the potential to recognize synaptic anomalies and chromosome-specific structural and behavioural characteris-tics. We confirm these potentials by the recognition of the heterologous synapsis of the X and Y chromosomes and bythe variances of synaptonemal complex lengths for each of the colour-coded bivalents in eight prophase nuclei.

Key words: SKY, meiosis, synaptonemal complex, multicolour, chromosome painting, spectral karyotyping, protein–SKYco-detection.

Résumé: Le caryotypage spectral, c’est-à-dire une hybridation in situ à l’aide de sondes spécifiques de chaque chro-mosome, permet d’assigner une couleur à chacun des 21 chromosomes mitotiques chez la souris. Les auteurs ont modi-fié cette technique pour l’étude de chromosomes en prophase méiotique, et les résultats indiquent que chacun desbivalents en pachytène ou en métaphase I peut être identifié. Cette technique offrirait la possibilité d’observer des ano-malies synaptiques ainsi que des caractéristiques structurales ou des comportements qui sont spécifiques d’un chromo-some précis. Les auteurs ont confirmé ces possibilités en visualisant les synapses hétérologues entre chromosomes X etY de même qu’en observant la variance quant à la longueur des complexes synaptonémiques pour chaque paire de bi-valents (distingués en fonction de leur couleur) au sein de huit noyaux en prophase.

Mots clés: SKY, méiose, complexe synaptonémique, multicolore, coloration chromosomique, caryotypage spectral, co-détection protéine–SKY.

[Traduit par la Rédaction] Heng et al. 298

Introduction

At prophase of meiosis, the chromosomes acquire meiosis-specific structures and behaviours that function in homologoussynapsis, recombination, and segregation. Experimentally in-duced defects in one or more factors that regulate meiosis inthe mouse, such as DMC1–/– (Pittman et al. 1998), SCP3–/–(Yuan et al. 2000), SPO11–/– (Baudat et al. 2000), andATM–/– (Barlow et al. 1998), have been reported to affectsynapsis. If there is interference with the induction of DNAbreaks (SPO11–/–) or the homology search mechanism iscompromised (DMC1–/–), it can be expected that synapsisof homologous chromosomes will be reduced or absent.However, significant numbers of synaptonemal complexes(SCs) have been observed in such cases. The SCs may beproduced in spite of reduced homology recognition

mechanisms or alternately they involve nonhomologous asso-ciations.

To differentiate between these alternatives, we explore thepossibility of adapting the spectral karyotyping (SKY)multicolour technique, developed for colour coding mitoticchromosomes in human or mouse (Liyanage et al. 1996), tothe colour coding of mouse meiotic prophase chromosomes.Modifications are necessary to accommodate the meioticspecific conditions that include the lesser degree ofchromatin compaction and the simultaneous visualization ofthe chromosome cores and SCs.

We show that the SKY procedure can effectively be usedto differentiate each of the meiotic prophase chromosomesand their SCs. The detection of nonhomologous associationis demonstrated by the two-colour signal of the X–Ychromosome pair, and the identification of individual chromo-

Genome44: 293–298 (2001) © 2001 NRC Canada

293

DOI: 10.1139/gen-44-2-293

Received December 1, 2000. Accepted February 9, 2001. Published on the NRC Research Press Web site March 23, 2001.

Corresponding Editor: T. Schwarzacher.

H.H.Q. Heng,1 G. Liu, W. Lu, S. Bremer, and M. Hughes. Center for Molecular Medicine and Genetics, Department ofPathology, Karmanos Cancer Institute, 5047 Gullen Mall, 5107 Biological Science Building, Wayne State University School ofMedicine, Detroit, MI 48202, U.S.A.C.J. Ye. SeeDNA Biotech Inc., Windsor, ON, Canada.P. Moens.Department of Biology, York University, Toronto, ON M3J 1P3, Canada.

1Corresponding author (e-mail: [email protected]).

I:\gen\gen44\gen-02\G01-018.vpWednesday, March 21, 2001 8:27:09 AM

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somes is explored in a comparative analysis of eight completeprophase nuclei.

Materials and methods

Meiotic chromosome preparationTesticular cells were obtained from 3- to 6-month-old mice.

Methanol – acetic acid fixationTubular fragments from a macerated testis in minimal essential

medium (MEM) were allowed to settle in an Eppendorf tube. Thecell suspension was removed to a clean Eppendorf tube, and thecells were pelleted by centrifugation at 1500 rpm for 3 min. Cellswere collected, hypotonically treated with 0.4% KCl for 10 min,and fixed in either 3:1 or 2:1 methanol – acetic acid. After threechanges of fixative, the chromosome preparations were made bydropping the cell suspension onto a cold slide, which was then airdried (Heng and Tsui 1993). Slides were baked for a few hoursthen used immediately for SKY.

Paraformaldehyde fixationFollowing cell preparation as indicated in the previous section,

the MEM was drained from the Eppendorf tube followingcentrifugation, and the cells were gently resuspended in the resid-ual liquid. Five microlitres of this suspension was touched to thesurface of a bath containing 0.5% NaCl, pH 8, and the nuclei werecollected on a clean glass slide. The slides were fixed first inparaformaldehyde with 0.03% SDS at a pH of 8.2; then inparaformaldehyde, pH 8.2, followed by three washes in 0.4% Ko-dak Photo-Flo 200, pH 8, for 1 min each. Slides were briefly airdried and used immediately for SKY or stored at 20°C for later use(Heng et al. 1994, 2000).

Immunostaining of the centromeres and synaptonemalcomplexes

Slides with paraformaldehyde-fixed nuclei were incubated inthree changes of blocking buffer (PBS with 10% v/v antibody dilu-tion buffer (ADB: 10% goat serum, 3% BSA, 0.05% Triton X-100in PBS), and 0.4% Kodak Photo-Flo) for 10 min each. The secondwash also contained 0.01% Triton X-100. Appropriate dilutions ofprimary antibody were added to the slides (in this case, anti-COR1and anti-SYN1 and the anticentromeric serum, CREST) whichwere incubated at 37°C for 2 h or overnight at room temperature(Dobson et al. 1994). Following washes in a blocking buffer seriesas described for primary antibody treatment, the nuclei were incu-bated in appropriate dilutions of the pertinent secondary antibodiestagged with a variety of fluorochromes or gold particles. To com-pare the results of different combinations of SC detection and SKYpainting, three different secondary antibody tags (fluoresceinisothiocyanate (FITC), rhodamine, and gold staining) were used tostain the SC. Following three 10-min washes in PBS with 0.4%Photo-Flo and two 1-min rinses in distilled water with 0.4% Photo-Flo, the slides were dried and were ready for SKY detection.

SKY detection

Slide treatmentMethanol – acetic acid fixed slides and whole-mount surface

spreads with paraformaldehyde-fixed meiotic chromosomes, someof which were prestained with antibody and fluorochromes, wereused for comparison. Slides were incubated at 37°C in pepsin solu-tion (0.025 g/mL) for 1 min. After two washings with 1× PBS, fol-lowed by 1× PBS containing 50 mM MgCl, the slides were fixedwith 1% formaldehyde for 10 min. Slides were then dehydratedwith ethanol (70%, 90%, and 100%) and air dried following an ad-ditional wash in 1× PBS.

DenaturationSlides were denatured using 70% formamide – 2× SSC at 72°C

for 90 s then immediately immersed for 2 min each in cold 70%,80%, and 100% ethanol. The SKY–paint mixture was denatured at80°C for 7 min following incubation at 37°C for 1 h.

HybridizationTen microlitres of denatured SKY–paint was loaded on the de-

natured slide. After sealing the edges of the cover slip with rubbercement, slides were transferred to a humidified chamber and incu-bated at 37°C for 48–96 h.

DetectionSlides were washed with 50% formamide in 2× SSC for 5 min,

1× SSC for 2× 5 min, and then 4× SSC with 0.1% Tween 20 for2 min. Signals were detected by following the instructions of thedetection kit from Applied Spectral Imagining Inc. The slides werewashed, air dried, stained with 4′,6-diamino-2-phenylindole(DAPI), and mounted with antifade.

Image acquisition and analysisThe protocol for the SKY image was followed to acquire stan-

dard SKY images. We do not recommend the standard SKY imag-ing procedure for image acquisition of SCs and other proteinmarkers such as centromeres. Although some well-spread meioticfigures could be used to obtain chromosome contours with thestandard SKY program, we elected to utilize colour images takenwith the SKY filter only rather than the DAPI filter in order to ob-tain better images of the SC. Specifically, after taking a colourphotograph of the protein-stained image, a second photograph inblack and white was taken using the “DAPI” option for picture ac-quisition, but the filter was not changed to DAPI as advised forstandard SKY images. Thus the same filter is used for both theDAPI and the spectral colour image. The SCs were stained by anti-COR1 and detected by FITC. The lengths of SCs for each spreadwere measured on the computer screen.

Results

SKY chromosome painting of meiotic prophase nucleiThe appearance of SKY staining of relatively undisturbed

meiotic prophase nuclei is demonstrated in Fig. 1. TheCREST anti-centromere immune staining serves as a guideto the early developmental stages. At the leptotene stagewhere most of the chromosomes and the 40 centromeres arenot paired (Figs. 1a and 1f), the colours are relatively dif-fuse, indicating that no sharply defined domains are as yetestablished. Somewhat later (Figs. 1b and 1g), there arefewer centromeric signals as a result of chromosomesynapsis. The chromosome domains are somewhat moreclearly defined than at leptotene. At early pachytene(Figs. 1c and 1h) the individual bivalents have become moredistinct and they are well defined at late pachytene where thechromosomes are compacted and relatively short (Figs. 1dand 1i). The effectiveness of the SKY procedure at meiosisis demonstrated in Figs. 1e and 1f where the SKY programcan identify each bivalent by its specific colour.

SKY identification of individual pachytenechromosomes

In whole-mount testicular cell preparations with well-spread pachytene chromosomes, each bivalent has a specificcolour (Fig. 2a). The SCs and associated chromatin areshown in Fig. 2b. The colours of Fig. 2a are interpreted by

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the SKY program and then expressed in standardized col-our-coded chromosome images (Fig. 2c). The SKY imagesand the SCs of Fig. 2c are presented in a sorted karyotype in

Fig. 3a, which is compared with the chromosomes or SCs ofa second nucleus in Fig. 3b. It is evident from this and fromsix additional nuclei that SKY-painted mouse pachytenekaryotypes do not consistently agree with the order definedby the mitotic chromosomes (Table 1; Fig. 3). The artefactualand possible real causes of the discrepancies are discussed below.

Technical aspectsThe SKY program was designed for the analysis of con-

densed mitotic chromosomes, and some modifications had tobe introduced to successfully analyse the less condensed,more diffuse meiotic prophase chromosomes. The methanolfixation that is routinely used for mitotic chromosome prepa-rations proved to be less effective for pachytene chromo-somes. Instead, the paraformaldehyde fixation that isnormally used for meiotic chromosome spreads and for EMand immune staining gave better SKY-staining results. In ad-dition, it was found that extended hybridization times im-proved the SKY image.

The fluorochromes used for immune staining of chromo-some-associated proteins such as the chromosome cores andthe centromeres were found to be a source of optical inter-ference with the SKY-view analysis. Comparison of FITC,rhodamine, and gold-stained proteins indicated that FITCproduced the least interference. In addition, the dosage ofthe fluorochromes had to be kept low to minimize interfer-ence.

Discussion

There are numerous causes for synaptic failure and themispairing of chromosomes at meiotic prophase as refer-enced in the introduction. If the effects of mutations or me-tabolites on chromosome behaviour at meiosis are to beevaluated beyond the generality of “synaptic defects,” it isrequired, among others, to know to what extent homologyrecognition is reduced or abolished. Cytogenetically, synap-tic failure has been deduced from the presence of univalentsat late stages of meiotic prophase, or at early prophasestages, by observations on partially synapsed chromosomesor by partner switches of chromosome cores, usually withimmunofluorescence or electron microscopy.

To what extent associations are homologous or hetero-logous is not obvious unless additional identifiers are used.In the case of human, mouse, and rat meiotic chromosomes,

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Heng et al. 295

Fig. 1. Multicolour appearances of intact meiotic prophase nuclei(a to e) and the corresponding centromere and (or) chromatinimages (f to j). (a and f) An early stage prior to the pairing ofchromosomes with approximately 40 centromeric signals that aretypically fairly evenly distributed through the nuclear volume.The individual chromosomes do not have well-defined bound-aries at this stage. (b and g) The reduction in numbers ofcentromeric signals suggests that chromosome synapsis is inprogress. The chromosome domains have become more distinct.(c and h) At early pachytene, the synapsis is complete and thechromosome domains are well delineated. (d and i) At latepachytene, the chromosomes are more compacted and the indi-vidual domains are well separated. (e and j) A typical metaphase1 configuration where the colour coding of the individual biva-lents is evident. The nuclei are about 40µm in diameter.



individual chromosomes have been identified by chromo-some-specific probes, such as centromere- or telomere-specific probes, satellite DNA, ribosomal DNA, repeated or

unique sequences, or artificially introduced transgenes(Heng et al. 1994). With those aids it is potentially possibleto determine chromosome-specific activities in synapsis orrecombination in normal meiosis. For a complete analysis,however, each pair of homologous chromosomes should beindividually recognizable so that the levels of homologousand nonhomologous synapses can be assessed.

Multicolour spectral karyotyping (SKY) has provided ex-cellent identification of individual chromosomes and chro-mosome rearrangements in mitotic cells with a unique huefor each member of the set of 23 human and 21 mouse chro-

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Fig. 2. A demonstration of the colour-coded analysis of meioticprophase chromosomes. (a) The multicolour appearance of sur-face-spread pachytene chromosomes. (b) The SCs and associatedchromatin of the same chromosomes shown in 2a. (c) The colourcoding of the individual bivalents by the SKY-view program. Ofparticular interest is the demonstration of the heterologous asso-ciation between the X and Y chromosomes. The numbers corre-spond with those of the mitotic mouse karyotype. The length ofa medium size SC is about 10µm.

Fig. 3. The sorted SKY karyotypes and associated SCs of twopachytene nuclei. The average SC lengths and the standard devi-ations of eight such nuclei are reported in Table 1 and presentedas a histogram in Fig. 4.



mosomes (Liyanage et al. 1996; Schrock et al. 1996). Thesystem is extensively and successfully used in the detectionof chromosome abnormalities in cell lines and malignantgrowths (Liyanage et al. 1996; Liu et al. 2000; Ried et al.1998) but its application to meiotic prophase chromosomeswhere it can serve numerous purposes has so far not been re-ported. We demonstrate that multicolour fluorescent in situhybridization (FISH) can provide an unprecedented refine-ment in meiotic chromosome analysis with an example ofthe recognition of a heterologous association of the X and Ychromosomes and with the statistics of differential chromo-some compaction at meiotic prophase.

Detection of heterologiesWe anticipate that the SKY identification of individual

chromosomes will permit the quantification of mispairing atmeiotic prophase. In a number of gene disruptions, chromo-some synapsis is compromised (ATM–/–, SPO11–/–,DMC1–/–, SCP3–/–) but it is not clear if the occasional SCsare between homologous or heterologous chromosomes. Therecognition of a heterologous association by SKY analysis isdemonstrated here by the X–Y pair in Figs. 2 and 3. In theauthentic SKY colour in Fig. 2a and in the colour-coded im-age of Figs. 2c, 3a, and 3b, the juxtaposition of the two dif-ferent chromatin domains is clearly defined. From thisdemonstration it seem likely that the application of thismethodology can visualize the extent of homologous andnonhomologous synapsis in cases of disturbed meioticprophase.

Individual chromosome characteristicsObservations on meiotic prophase chromosomes suggest

that they do not progress through prophase in perfect syn-chrony. For example, some chromosomes have initiatedsynapsis before others, some are late in completing synapsis,some are arranged in a bouquet, others less so, and somelose their association with recombination proteins beforeothers (Moens et al. 1998). These traits are evident relativeto the average condition of all chromosomes in the same nu-cleus, and the question whether deviations from the averageare chromosome-specific traits or random events can be an-

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Heng et al. 297

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Fig. 4. Average SC lengths and standard deviations of colour-coded bivalents in eight mouse spermatocyte nuclei measured inarbitrary length units. From this relatively small sample, it wouldappear the chromosomes 5 and 15 are structurally less stablethan chromosomes 3, 8, 9, and 14. This type of analysis has notbeen feasible in the past as it depends on the individual identifi-cation of each chromosome.



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298 Genome Vol. 44, 2001

swered only if each chromosome can be identified. Tech-nically this has not been possible to date. It is in this respectthat the SKY procedure can bring new insight into structuraland functional aspects of meiotic prophase chromosomesduring their critical activities in synapsis, recombination,and disjunction.

As an example, we compare the meiotic SC karyotypes ofeight pachytene nuclei (Table 1; Fig. 4). The average SClengths of each chromosome in Fig. 4 show that there is ageneral tendency from long to short in agreement with themitotic assignments by the SKY analysis. However, withineach nucleus there is only a very general correspondence be-tween the meiotic SC length of a particular chromosome andits mitotic karyotype position (Table 1). The variation in to-tal lengths of all SCs in a meiotic nucleus (19–61 unitlengths in Table 1) is generally attributed to developmentalstage and to preparation effects (Moses et al. 1977).

While the variation in length of a particular bivalent rela-tive to the others within the same nucleus has been attributedexclusively to preparation techniques, the explanation hasnot been verified because of the inability to positively iden-tify particular chromosomes. In the present case, the relativepositions of chromosomes 5 and 15 are the most variablewithin the meiotic karyotype (Fig. 4). However, rather thancrediting preparation artifacts for this variation, these chro-mosomes may have a more flexible structure than the others.Conversely, chromosomes 3, 4, 8, 9, and 14 have small stan-dard deviations indicating less variable SC lengths, and pos-sibly a more rigid chromosome structure. A more extensivestudy of SCs in SKY colour-coded chromosomes may deter-mine if the differences in the variances are fortuitous or in-dicative of inherent differences in chromosome structure.

Acknowledgements

This work was supported by the start-up fund for H.H.from the Center for Molecular Medicine and Genetics, WayneState School of Medicine and by the Natural Sciences andEngineering Research Council of Canada for P.M. Additionalsupport was provided by the Genomics/Genetics core of theKarmanos Cancer Institute. We thank Barbara Spyropoulosfor her help in the preparation of this manuscript.

References

Barlow, C., Liyanage, M., Moens, P.B., Tarsounas, M., Nagashima,K., Brown, K., Rottinghaus, S., Jackson, S.P,. Tangle, D., Ried,T., and Wynshaw-Boris, A. 1998. Atm deficiency results in se-

vere meiotic disruption as early as leptonema of prophase I.Development (Cambridge),125: 4007–4017.

Baudat, F., Manova, K., Yuen, J.P., Jasin, M., and Keeney, S. 2000.Chromosome synapsis defects and sexual dimorphic meioticprogression in mice lacking spo11. Mol. Cell,6: 989–998.

Dobson, M.J., Pearlman, R.E., Karaiskakis, A., Spyropoulos, B.,and Moens, P.B. 1994. Synaptonemal complex proteins: occur-rence, epitope mapping and chromosome disjunction. J. CellSci. 107: 2749–2760.

Heng, H.H.Q., and Tsui, L.-C. 1993. Modes of DAPI banding andsimultaneous in situ hybridization. Chromosoma (Berlin),102:325–332.

Heng, H.H.Q., Tsui, L.-C., and Moens, P.B. 1994. Organization ofheterologous DNA inserts on the mouse meiotic chromosomecore. Chromosoma (Berlin),103: 401–407.

Heng, H.H.Q., Spyropoulos, B., and Moens, P.B. 2000. DNA-protein in situ co-detection.In Methods in molecular biology: Insitu hybridization protocols.Edited by I.A. Darby. HumanaPress, Totowa, N.J. pp. 15–27.

Liu, G., Lu, W., Bremer, S., Hameister, H., Scheriner, B., Hughes,M., and Heng, H.H.Q. 2000. Spectral karyotyping of mouse cellline WMP2. Cytogenet. Cell Genet.90: 271–274.

Liyanage, M., Coleman, A., Dumanoir, S., Veldman, T.,McCormack, S., Dickson, R., Barlow, B., Wynshaw-Boris, A.,Janz, S., Wienberg, J., Ferguson-Smith, M.A., Schrock, E., andRied, T. 1996. Multicolour spectral karyotyping of mouse chro-mosomes. Nature Genet.14: 312–315.

Moens, P.B., Pearlman, R.E., Heng, H.H.Q., and Traut, W. 1998.Chromosome cores and chromatin at meiotic prophase.In Meio-sis and gametogenesis.Edited byM.A. Handel. Academic Press,San Diego, Calif. pp. 241–262.

Moses, M.J., Slatton, G.H., Gambling, T.M., and Starmer, C.F.1977. Synaptonemal complex karyotyping in spermatocytes ofthe Chinese hamster (Cricetulus griseus). III. Quantitative Eval-uation. Chromosoma (Berlin),60: 345–375.

Pittman, D.L., Cobb, J., Schimenti, K.J., Wilson, L.A., Cooper,D.M., Brignull, E., Handel, M.A., and Schimenti, J.C. 1998.Meiotic prophase arrest with failure of chromosome synapsis inmice deficient for Dmc1, a germline specific RecA homolog.Mol. Cell. 5: 697–705.

Ried, T., Schrock, E., Ning, Y., and Wienberg, J. 1998. Chromo-some painting: a useful art. Hum. Mol. Genet.7: 1619–1626.

Schrock, E., Du Manoir, S., Veldman, T., Schoell, B., Wienberg, J.,Ferguson-Smith, M.A., Ning, Y., Ledbetter, D.H., Bar-Am, I.,Soenksen, D., Garini, Y., and Ried, T. 1996. Multicolor spectralkaryotyping of human chromosomes. Science (Washington,D.C.), 273: 494–497.

Yuan, L., Liu, J.G., Zhao, J., Brundell, E., Daneholt, B., and Hoog,C. 2000. The murine SCP3 gene is required for synaptonemalcomplex assembly, chromosome synapsis, and male fertility.Mol. Cell, 5: 73–83.



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