TY - JOUR
T1 - Phenotypic Analysis of Dominant Mutant Effects in Mice
AU - Papaioannou, Virginia E.
AU - Behringer, Richard R.
N1 - Publisher Copyright:
© 2024 Cold Spring Harbor Laboratory Press.
PY - 2024/1
Y1 - 2024/1
N2 - Dominant effects of a mutation may show up at any time during a mutational analysis, including during the early stages of an embryonic stem (ES) cell gene targeting experiment. Here, we discuss the mechanisms of dominant and semidominant effects and how they might appear if they show up in heterozygous ES cells, in ES cell chimeras, or in heterozygous progeny of chimeras. Similarly, dominant effects may be seen in mice heterozygous for CRISPR-Cas-targeted, -induced, or spontaneous mutations. If the dominant effects prevent the germline transmission of ES cells or cause fertility problems in heterozygotes, they can severely limit further analysis of the mutation. Ways to circumvent such reproductive problems are presented. The special case of imprinted genes, which may be functionally hemizygous and present a different phenotype when inherited from the mother than when inherited from the father, is discussed.
AB - Dominant effects of a mutation may show up at any time during a mutational analysis, including during the early stages of an embryonic stem (ES) cell gene targeting experiment. Here, we discuss the mechanisms of dominant and semidominant effects and how they might appear if they show up in heterozygous ES cells, in ES cell chimeras, or in heterozygous progeny of chimeras. Similarly, dominant effects may be seen in mice heterozygous for CRISPR-Cas-targeted, -induced, or spontaneous mutations. If the dominant effects prevent the germline transmission of ES cells or cause fertility problems in heterozygotes, they can severely limit further analysis of the mutation. Ways to circumvent such reproductive problems are presented. The special case of imprinted genes, which may be functionally hemizygous and present a different phenotype when inherited from the mother than when inherited from the father, is discussed.
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U2 - 10.1101/pdb.over107978
DO - 10.1101/pdb.over107978
M3 - Review article
C2 - 37932089
AN - SCOPUS:85181586715
SN - 1940-3402
VL - 2024
JO - Cold Spring Harbor protocols
JF - Cold Spring Harbor protocols
IS - 1
ER -