Skip to main content
PMC home page
Journal of Anatomy logoLink to Journal of Anatomy
. 1995 Jun;186(Pt 3):607–617.

Craniofacial abnormalities in homozygous Small eye (Sey/Sey) embryos and newborn mice.

M H Kaufman 1, H H Chang 1, J P Shaw 1
PMCID: PMC1167018  PMID: 7559133

Abstract

The Small eye (Sey) gene in the mouse is lethal in the homozygous state. It is located on chromosome 2, is a mutation in the Pax-6 gene, and is genetically homologous with the human aniridia 2 (AN2) gene mutation. Numerous studies over the last few years, using genetic and molecular biological approaches, have investigated both the location of the gene as well as its possible mode of action. In the homozygous state, the primary defect appears to be limited to the failure of differentiation of the presumptive lens and nasal placodes. Such mice therefore display a characteristic phenotype; they possess neither eyes nor any nasal derivatives. Their heterozygous (Sey/+) and normal (+/+) littermates may be distinguished before birth only by a detailed examination of their eyes. Few detailed morphological/histological studies have been undertaken to date in the Sey/Sey embryos and newborn, and in the present study we describe a variety of craniofacial abnormalities that have not previously been reported. We observed, with one exception, delayed closure of the palate, and the presence in 80% of mice of an abnormal complement of upper incisor teeth, so that 35% possessed 1 supernumerary tooth while 45% possessed 2 supernumerary teeth. In these mice, a total of either 3 or 4, rather than the normal complement of 2, upper incisor teeth were present. Possibly the most unexpected finding, however, was the presence of a median cartilaginous rod-like structure which protruded between the 2 maxillae to give the Alizarin red S and Alcian blue-stained 'cleared' skulls of the newborn mice a characteristic 'unicorn-like' appearance. While this structure appeared to be a rostral extension of the chondrocranium, its exact derivation is unclear.

Full text

PDF
608

Images in this article

609Fig. 1
on p.609
610Fig. 2
on p.610
611Fig. 3
on p.611
612Fig. 4
on p.612
613Fig. 5
on p.613
614Fig. 6
on p.614

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. DOEGE T. C., THULINE H. C., PRIEST J. H., NORBY D. E., BRYANT J. S. STUDIES OF A FAMILY WITH THE ORAL-FACIAL-DIGITAL SYNDROME. N Engl J Med. 1964 Nov 19;271:1073–1078. doi: 10.1056/NEJM196411192712101. [DOI] [PubMed] [Google Scholar]
  2. GARDNER E. J. Follow-up study of a family group exhibiting dominant inheritance for a syndrome including intestinal polyps, osteomas, fibromas and epidermal cysts. Am J Hum Genet. 1962 Dec;14:376–390. [PMC free article] [PubMed] [Google Scholar]
  3. GORLIN R. J., PSAUME J. Orodigitofacial dysostosis--a new syndrome. A study of 22 cases. J Pediatr. 1962 Oct;61:520–530. doi: 10.1016/s0022-3476(62)80143-7. [DOI] [PubMed] [Google Scholar]
  4. Glaser T., Lane J., Housman D. A mouse model of the aniridia-Wilms tumor deletion syndrome. Science. 1990 Nov 9;250(4982):823–827. doi: 10.1126/science.2173141. [DOI] [PubMed] [Google Scholar]
  5. Hanson I. M., Fletcher J. M., Jordan T., Brown A., Taylor D., Adams R. J., Punnett H. H., van Heyningen V. Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly. Nat Genet. 1994 Feb;6(2):168–173. doi: 10.1038/ng0294-168. [DOI] [PubMed] [Google Scholar]
  6. Hill R. E., Favor J., Hogan B. L., Ton C. C., Saunders G. F., Hanson I. M., Prosser J., Jordan T., Hastie N. D., van Heyningen V. Mouse small eye results from mutations in a paired-like homeobox-containing gene. Nature. 1991 Dec 19;354(6354):522–525. doi: 10.1038/354522a0. [DOI] [PubMed] [Google Scholar]
  7. Hodgson S. V., Saunders K. E. A probable case of the homozygous condition of the aniridia gene. J Med Genet. 1980 Dec;17(6):478–480. doi: 10.1136/jmg.17.6.478. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hogan B. L., Hirst E. M., Horsburgh G., Hetherington C. M. Small eye (Sey): a mouse model for the genetic analysis of craniofacial abnormalities. Development. 1988;103 (Suppl):115–119. doi: 10.1242/dev.103.Supplement.115. [DOI] [PubMed] [Google Scholar]
  9. Hogan B. L., Horsburgh G., Cohen J., Hetherington C. M., Fisher G., Lyon M. F. Small eyes (Sey): a homozygous lethal mutation on chromosome 2 which affects the differentiation of both lens and nasal placodes in the mouse. J Embryol Exp Morphol. 1986 Sep;97:95–110. [PubMed] [Google Scholar]
  10. Jowett A. K., Vainio S., Ferguson M. W., Sharpe P. T., Thesleff I. Epithelial-mesenchymal interactions are required for msx 1 and msx 2 gene expression in the developing murine molar tooth. Development. 1993 Feb;117(2):461–470. doi: 10.1242/dev.117.2.461. [DOI] [PubMed] [Google Scholar]
  11. Krauss S., Johansen T., Korzh V., Fjose A. Expression pattern of zebrafish pax genes suggests a role in early brain regionalization. Nature. 1991 Sep 19;353(6341):267–270. doi: 10.1038/353267a0. [DOI] [PubMed] [Google Scholar]
  12. Li H. S., Yang J. M., Jacobson R. D., Pasko D., Sundin O. Pax-6 is first expressed in a region of ectoderm anterior to the early neural plate: implications for stepwise determination of the lens. Dev Biol. 1994 Mar;162(1):181–194. doi: 10.1006/dbio.1994.1077. [DOI] [PubMed] [Google Scholar]
  13. Lumsden A. G., Buchanan J. A. An experimental study of timing and topography of early tooth development in the mouse embryo with an analysis of the role of innervation. Arch Oral Biol. 1986;31(5):301–311. doi: 10.1016/0003-9969(86)90044-0. [DOI] [PubMed] [Google Scholar]
  14. Lumsden A. G. Spatial organization of the epithelium and the role of neural crest cells in the initiation of the mammalian tooth germ. Development. 1988;103 (Suppl):155–169. doi: 10.1242/dev.103.Supplement.155. [DOI] [PubMed] [Google Scholar]
  15. Lyon M. F., Phillips R. J., Fisher G. Dose-response curves for radiation-induced gene mutations in mouse oocytes and their interpretation. Mutat Res. 1979 Nov;63(1):161–173. doi: 10.1016/0027-5107(79)90113-1. [DOI] [PubMed] [Google Scholar]
  16. MEYER D. B., O'RAHILLY R. Multiple techniques in the study of the onset of prenatal ossification. Anat Rec. 1958 Oct;132(2):181–193. doi: 10.1002/ar.1091320207. [DOI] [PubMed] [Google Scholar]
  17. MacKenzie A., Ferguson M. W., Sharpe P. T. Expression patterns of the homeobox gene, Hox-8, in the mouse embryo suggest a role in specifying tooth initiation and shape. Development. 1992 Jun;115(2):403–420. doi: 10.1242/dev.115.2.403. [DOI] [PubMed] [Google Scholar]
  18. MacKenzie A., Ferguson M. W., Sharpe P. T. Hox-7 expression during murine craniofacial development. Development. 1991 Oct;113(2):601–611. doi: 10.1242/dev.113.2.601. [DOI] [PubMed] [Google Scholar]
  19. Mackenzie A., Leeming G. L., Jowett A. K., Ferguson M. W., Sharpe P. T. The homeobox gene Hox 7.1 has specific regional and temporal expression patterns during early murine craniofacial embryogenesis, especially tooth development in vivo and in vitro. Development. 1991 Feb;111(2):269–285. doi: 10.1242/dev.111.2.269. [DOI] [PubMed] [Google Scholar]
  20. Matsuo T., Osumi-Yamashita N., Noji S., Ohuchi H., Koyama E., Myokai F., Matsuo N., Taniguchi S., Doi H., Iseki S. A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells. Nat Genet. 1993 Apr;3(4):299–304. doi: 10.1038/ng0493-299. [DOI] [PubMed] [Google Scholar]
  21. Payne A. P. The harderian gland: a tercentennial review. J Anat. 1994 Aug;185(Pt 1):1–49. [PMC free article] [PubMed] [Google Scholar]
  22. Püschel A. W., Gruss P., Westerfield M. Sequence and expression pattern of pax-6 are highly conserved between zebrafish and mice. Development. 1992 Mar;114(3):643–651. doi: 10.1242/dev.114.3.643. [DOI] [PubMed] [Google Scholar]
  23. Sperber G. H. Genetic mechanisms and anomalies in odontogenesis. J Can Dent Assoc (Tor) 1967 Aug;33(8):433–442. [PubMed] [Google Scholar]
  24. Theiler K., Varnum D. S. Development of coloboma (Cm/+), a mutation with anterior lens adhesion. Anat Embryol (Berl) 1981;162(1):121–126. doi: 10.1007/BF00318098. [DOI] [PubMed] [Google Scholar]
  25. Theiler K., Varnum D. S., Stevens L. C. Development of Dickie's small eye, a mutation in the house mouse. Anat Embryol (Berl) 1978 Dec 5;155(1):81–86. doi: 10.1007/BF00315732. [DOI] [PubMed] [Google Scholar]
  26. Theiler K., Varnum D. S., Stevens L. C. Development of Dickie's small eye: an early lethal mutation in the house mouse. Anat Embryol (Berl) 1980;161(1):115–120. doi: 10.1007/BF00304672. [DOI] [PubMed] [Google Scholar]
  27. Ton C. C., Miwa H., Saunders G. F. Small eye (Sey): cloning and characterization of the murine homolog of the human aniridia gene. Genomics. 1992 Jun;13(2):251–256. doi: 10.1016/0888-7543(92)90239-o. [DOI] [PubMed] [Google Scholar]
  28. Walther C., Gruss P. Pax-6, a murine paired box gene, is expressed in the developing CNS. Development. 1991 Dec;113(4):1435–1449. doi: 10.1242/dev.113.4.1435. [DOI] [PubMed] [Google Scholar]
  29. van der Meer-de Jong R., Dickinson M. E., Woychik R. P., Stubbs L., Hetherington C., Hogan B. L. Location of the gene involving the small eye mutation on mouse chromosome 2 suggests homology with human aniridia 2 (AN2). Genomics. 1990 Jun;7(2):270–275. doi: 10.1016/0888-7543(90)90550-e. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Anatomy are provided here courtesy of Anatomical Society of Great Britain and Ireland

RESOURCES