Somatic cells, germ cells and cell lines derived from a PTTG knockout rodent

Abstract

Disclosed is a null mutant (or knockout) rodent comprising in its germ cells an artificially induced PTTG null mutation. In some embodiments, the null mutant rodent can be generated by way of homologous recombination in an embryonic stem cell or germ cell. The inventive null mutant rodent can be used to study mammalian physiology at the cellular, tissue, and/or organismal level with respect to various phenotypes, including hyperglycemia, hypoinsulinaemia, hypoleptinemia, diabetes, chromosomal aneuploidy, premature centromere division, chromosomal damage, aberrant mitotic cellular division, thrombocytopenia, thymic hyperplasia, splenic hypoplasia, testicular hypoplasia, and female subfertility. Also disclosed is an animal model for diabetes. Also disclosed is a somatic or germ cell obtained from the null mutant rodent. Also disclosed is a cell line derived from a cell obtained from the null mutant rodent.

1 - 20 . (canceled)  
     
     
         21 . A somatic cell obtained from a null mutant mouse comprising in its germ cells an artificially induced Pituitary tumor transforming gene (PTTG) null mutation on both PTTG alleles, wherein said mutation results in said mouse exhibiting at least one Phenotype selected from the group consisting of hyperglycemia, hypoinsulinaemia, hypoleptinemia, diabetes, chromosomal aneuploidy, premature centromere division, chromosomal damage, aberrant mitotic cellular division, thrombocytopenia, thymic hyperplasia, splenic hypoplasia, testicular hypoplasia, and female subfertility, the prevalence of which is greater than in a mouse lacking said mutation.  
     
     
         22 . A cell line derived from the cell of  claim 21 .  
     
     
         23 . A cell line derived from a cell obtained from a null mutant mouse comprising in its germ cells an artificially induced pituitary tumor transforming gene (PTTG) null mutation on both PTTG alleles, wherein said mutation results in said mouse exhibiting at least one phenotype selected from the group consisting of hyperglycemia, hypoinsulinaemia, hypoleptinemia, diabetes, chromosomal aneuploidy, premature centromere division, chromosomal damage, aberrant mitotic cellular division, thrombocytopenia, thymic hyperplasia, splenic hypoplasia, testicular hypoplasia, and female subfertility, the prevalence of which is greater than in a mouse lacking said mutation.  
     
     
         24 . A germ cell obtained from a null mutant mouse comprising in its germ cells an artificially induced pituitary tumor transforming gene (PTTG) null mutation on both PTTG alleles, wherein said mutation results in said mouse exhibiting at least one phenotype selected from the group consisting of hyperglycemia, hypoinsulinaemia, hypoleptinemia, diabetes, chromosomal aneuploidy, premature centromere division, chromosomal damage, aberrant mitotic cellular division, thrombocytopenia, thymic hyperplasia, splenic hypoplasia, testicular hypoplasia, and female subfertility, the prevalence of which is greater than in a mouse lacking said mutation.  
     
     
         25 - 36 . (canceled)  
     
     
         37 . The somatic cell of  claim 21 , wherein functional PTTG protein is not expressed in the somatic cells of said mouse.  
     
     
         38 . The somatic cell of  claim 21 , wherein the cells of said mouse lack the ability to endogenously express functional PTTG protein.  
     
     
         39 . The somatic cell of  claim 21 , wherein both PTTG genes in said mouse have been artificially mutated by way of homologous recombination.  
     
     
         40 . The somatic cell of  claim 21 , wherein the PTTG null mutant mouse was generated by a mating of a male mouse and female mouse each bearing at least one artificially mutated PTTG allele.  
     
     
         41 . The somatic cell of  claim 40 , wherein said at least one mutated PTTG allele is generated by way of a technique selected from the group consisting of homologous recombination in an embryonic stem cell, site specific recombination, transpositional recombination, a frame shift mutation, and homologous recombination in a germ cell.  
     
     
         42 . The somatic cell of  claim 40 , wherein said at least one mutated PTTG allele contains a deletion of a segment selected from the group consisting of the translation start site, the KOZAK region, a segment of the endogenous PTTG gene promoter region, the transcription start codon, and combinations thereof.  
     
     
         43 . The cell line of  claim 23 , wherein the cells of said mouse lack the ability to endogenously express functional PTTG protein.  
     
     
         44 . The cell line of  claim 23 , wherein both PTTG genes in said mouse have been artificially mutated by way of homologous recombination.  
     
     
         45 . The cell line of  claim 23 , wherein the PTTG null mutant mouse was generated by a mating of a male mouse and female mouse each bearing at least one artificially mutated PTTG allele.  
     
     
         46 . The cell line of  claim 45 , wherein said at least one mutated PTTG allele is generated by way of a technique selected from the group consisting of homologous recombination in an embryonic stem cell, site specific recombination, transpositional recombination, a frame shift mutation, and homologous recombination in a germ cell.  
     
     
         47 . The cell line of  claim 45 , wherein said at least one mutated PTTG allele contains a deletion of a segment selected from the group consisting of the translation start site, the KOZAK region, a segment of the endogenous PTTG gene promoter region, the transcription start codon, and combinations thereof.  
     
     
         48 . The germ cell of  claim 24 , wherein the cells of said mouse lack the ability to endogenously express functional PTTG protein.  
     
     
         49 . The germ cell of  claim 24 , wherein both PTTG genes in said mouse have been artificially mutated by way of homologous recombination.  
     
     
         50 . The germ cell of  claim 24 , wherein the PTTG null mutant mouse was generated by a mating of a male mouse and female mouse each bearing at least one artificially mutated PTTG allele.  
     
     
         51 . The germ cell of  claim 50 , wherein said at least one mutated PTTG allele is generated by way of a technique selected from the group consisting of homologous recombination in an embryonic stem cell, site specific recombination, transpositional recombination, a frame shift mutation, and homologous recombination in a germ cell.  
     
     
         52 . The germ cell of  claim 50 , wherein said at least one mutated PTTG allele contains a deletion of a segment selected from the group consisting of the translation start site, the KOZAK region, a segment of the endogenous PTTG gene promoter region, the transcription start codon, and combinations thereof.