Methods for maintaining genetic stability of inbred animal strains

Abstract

The present invention provides novel methods of maintaining genetic stability of non-human animal inbred strains. In the methods, pedigree-tracked cryopreserved embryos derived from a foundation colony are produced and used to re-establish the foundation colony at appropriate intervals.

1 - 56 . (canceled) 
     
     
         57 . A genetically stabilized inbred rodent strain made by
 (a) establishing a foundation colony of an inbred rodent strain, wherein the foundation colony comprises only brother-sister pairs, parent-offspring pairs or brother-sister pairs and parent-offspring pairs from which all subsequent rodents of the strain are derived;   (b) maintaining a pedigree-tracked stock of cryopreserved rodent embryos, wherein the cyropreserved rodent embryos are obtained from a brother-sister pair or a parent-offspring pair from the foundation colony established in step (a);   (c) producing live rodents from cryopreserved rodent embryos of the pedigree-tracked stock obtained in step (b);   (d) selecting a pedigreed inbred breeding pair from the live rodents obtained in step (c) to be used as a new founder pair to re-establish the foundation colony, wherein the inbred breeding pair is a brother sister pair or a parent-offspring pair from which all subsequent rodents of the strain are derived;   (e) breeding the new founder pair obtained in step (d) to produce offspring and thereby re-establish the foundation colony wherein the foundation colony comprises only brother-sister pairs, parent-offspring pairs or brother-sister pairs and parent-offspring pairs from which all subsequent rodents of the strain are derived; and   (f) replenishing the foundation colony by repeating steps (c) to (e) at intervals of 1 to 20 generations and, thus, inhibiting the accumulation of genotypic changes, thereby maintaining genetic stability of the inbred rodent strain.   
     
     
         58 . (canceled) 
     
     
         59 . The genetically stabilized non-human animal inbred rodent strain of  claim 57  wherein the rodent is mouse. 
     
     
         60 . A genetically stabilized inbred rodent strain made by
 (a) establishing a foundation colony of an inbred rodent strain, wherein the foundation colony comprises only brother-sister pairs, parent-offspring pairs or brother-sister pairs and parent-offspring pairs from which all subsequent rodents of the strain are derived;   (b) maintaining a pedigree-tracked stock of cryopreserved rodent gametes or pre-gametes, wherein the cryopreserved rodent gametes or pre-gametes are obtained from a brother-sister pair or a parent-offspring pair from the foundation colony established in step (a);   (c) thawing and transplanting cryopreserved pedigree-tracked stock pre-gametes obtained in step (b) to produce pedigree-tracked male and/or female gametes;   (d) breeding the pedigree-tracked male and female gametes obtained in step (b) and/or (c) to produce pedigree-tracked embryos;   (e) producing live rodents from pedigree-tracked embryos obtained in step (d);   (f) selecting a pedigreed inbred breeding pair from the live rodents obtained in step (e) to be used as a new founder pair to re-establish the foundation colony, wherein the inbred breeding pair is a brother sister pair or a parent-offspring pair from which all subsequent rodents of the strain are derived;   (g) breeding the new founder pair obtained in step (f) to produce offspring and thereby re-establish the foundation colony wherein the foundation colony comprises only brother-sister pairs, parent-offspring pairs or brother-sister pairs and parent-offspring pairs from which all subsequent rodents of the strain are derived; and   (h) replenishing the foundation colony by repeating steps (c) to (g) at intervals of 1 to 20 generations and, thus, inhibiting the accumulation of genotypic changes, thereby maintaining genetic stability of the inbred strain.   
     
     
         61 . The genetically stabilized non-human animal inbred rodent strain of  claim 60  wherein the rodent is mouse. 
     
     
         62 . A genetically stabilized inbred rodent strain made by
 (a) establishing a foundation colony of an inbred mouse strain, wherein the foundation colony comprises only brother-sister pairs, parent-offspring pairs or brother-sister pairs and parent-offspring pairs from which all subsequent mice of the strain are derived;   (b) maintaining a pedigree-tracked stock of cryopreserved mouse embryonic stem cells, wherein the cryopreserved mouse embryonic stem cells are obtained from a brother-sister pair or a parent-offspring pair from the foundation colony established in step (a);   (c) thawing pedigree-tracked cryopreserved mouse embryonic stem cells obtained in step (b) and introducing the stem cells into host embryos to produce pedigree-tracked male and female gametes;   (d) breeding the pedigree-tracked male and female gametes obtained in step (c) to produce pedigree-tracked embryos;   (e) producing live mice from pedigree-tracked embryos obtained in step (d);   (f) screening the live mice to identify mice that are completely derived from the embryonic stem cells;   (g) selecting a pedigreed inbred breeding pair from the live mice identified in step (f) to be used as a new founder pair to re-establish the foundation colony, wherein the inbred breeding pair is a brother sister pair or a parent-offspring pair from which all subsequent mice of the strain are derived;   (h) breeding the new founder pair obtained in step (d) to produce offspring and thereby re-establish the foundation colony wherein the foundation colony comprises only brother-sister pairs, parent-offspring pairs or brother-sister pairs and parent-offspring pairs from which all subsequent mice of the strain are derived; and   (i) replenishing the foundation colony by repeating steps (c) to (h) at intervals of 1 to 20 generations and, thus, inhibiting the accumulation of genotypic changes, thereby maintaining genetic stability of the inbred strain.