ANS 378 Animal Genetics
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Research Journal Report #03
11/09/04
Research Topic: Lethal genes
Animal Species: Rat
Title of the Paper: Polydactyly lethal: a new mutant spontaneously occurring in the FPL strain of rats
Author(s): Aoyama, H.; Fujii, S.; Teramoto, S.; Shirasu, Y.
Abstract: A new mutant gene that causes preaxial polydactyly in the hindlimbs was found in the strain of rats with fused pulmonary lobes (fpl). Genetic analysis has revealed that the new mutation is inherited as an autosomal recessive trait and is not closely linked with the fpl gene. Since homozygous mutants die within the first 2 days after birth, the mutant gene was named polydactyly lethal, gene symbol pl. A test for allelism between the pl gene and another gene, pd, which also causes preaxial duplication anomalies, showed no allelism between these two genes. Skeletal examination revealed that all pl/pl newborns had thickening and/or bifurcation of tarsal I and metatarsal I, as well as duplication of the proximal and distal phalanges of digit I in the hindlimbs. In some cases, phalangeal duplication of bifurcation in digit I with thickening of metacarpal I was also found in the forelimbs, although extra forelimb digits were not detected externally. The pl/pl newborns showed hunchback-like abnormal posture externally and had several associated vertebral abnormalities in varying degrees, i.e., kyphosis, scoliosis, splitting of the thoracic vertebral bodies, and fusion of the lumbar vertebral bodies. No major malformations were seen in the visceral organs. The cause of neonatal deaths has not yet been determined.
Keywords: Genes, Lethal*
Foot deformities/*veterinary
Rats, Mutant Strains/*genetics
Alleles; Animals; Crosses, Genetic; Female; Foot Deformities/genetics; Genes, Recessive; Linkage (Genetics); Male; Pedigree; Rats
Reference: Aoyama, H., S. Fujii, S. Teramoto, and Y. Shirasu. 1991. Polydactyly lethal: a new mutant spontaneously occurring in the FPL strain of rats. J. of Hered. 82:397-401.
In rats, gene mutations that can cause congenital malformations are few. So when a mutation does occur, it is of great interest, because rats (as compared with other species such as mice) have the advantages of stable reproduction performance, less reaction to the stress of handling, and larger fetuses. These features make studies easier to perform. The authors of this paper have kept a Wistar-derived FPL strain of rats since 1978. These animals carry an autosomal recessive mutant gene known as fpl (fused pulmonary lobes). In 1988, two pups (in a litter of nine) exhibited polydactyly. This trait had never before been seen in the FPL group of rats, so it was believed to be caused by a spontaneous mutation. Both polydactyl pups from this litter died during the lactation period. Continued studies showed that homozygosity for the polydactyl lethal gene (tentatively being named pl) was lethal. Further matings were conducted using the original parental male and his progeny (since the original parental female was not available).
The purpose of this research was to try to describe the new mutant gene, to determine if it was linked with the fpl gene, and to test for allelism between the pl and pd (preaxial duplication) genes. Since this gene was a new mutant that, when homozygous, proves fatal, its study is of great interest. Information learned here may be able to be applied to other areas in the future.
Since both male and female pups were affected by this trait, the pl gene was determined to be autosomal and recessive. No linkage was found between the pl and fpl genes, and the pl and pd genes were not allelic. The pl gene itself (besides inducing death) also caused physical malformations and abnormal behavior in the pups. These included (in the hindlimbs) preaxial polydactyly, bilateral thickening and/or bifurcation of the tarsal I and metatarsal I, and duplication of the proximal and distal phalanges of digit I. Vertebral abnormalities were also documented, such as kyphosis, scoliosis, splitting of the ossification centers of thoracic vertebrae, and fusion of vertebrae in the lumbar region. Few problems were seen in the forelimbs, however in some cases there was a thickening of metacarpal I and a duplication or bifurcation of digit I. Pups also exhibited no righting reflex when placed on their backs, nor any suckling behavior.
It is always exciting when a new gene is found, especially when it is determined to have been a recent spontaneous mutation. The research involved in describing the new gene is very important, because it may lead to a better understanding of the way in which genes function and mutate. Having an opportunity like this occur in a species (in this case, the rat) which is easy to handle and a good candidate for more extensive research, is an added bonus. Information discovered in working with the pl gene can be added to our basic knowledge of genes and might eventually be able to be applied to other species as well.
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