RT Journal Article
SR Electronic
T1 Molecular Characterization of <em>Pax6<sup>2Neu</sup></em> Through <em>Pax6<sup>10Neu</sup></em>: An Extension of the <em>Pax6</em> Allelic Series and the Identification of Two Possible Hypomorph Alleles in the Mouse <em>Mus musculus</em>
JF Genetics
JO Genetics
FD Genetics Society of America
SP 1689
OP 1700
VO 159
IS 4
A1 Favor, Jack
A1 Peters, Heiko
A1 Hermann, Thomas
A1 Schmahl, Wolfgang
A1 Chatterjee, Bimal
A1 Neuhäuser-Klaus, Angelika
A1 Sandulache, Rodica
YR 2001
UL http://www.genetics.org/content/159/4/1689.abstract
AB Phenotype-based mutagenesis experiments will increase the mouse mutant resource, generating mutations at previously unmarked loci as well as extending the allelic series at known loci. Mapping, molecular characterization, and phenotypic analysis of nine independent Pax6 mutations of the mouse recovered in mutagenesis experiments is presented. Seven mutations result in premature termination of translation and all express phenotypes characteristic of null alleles, suggesting that Pax6 function requires all domains to be intact. Of major interest is the identification of two possible hypomorph mutations: Heterozygotes express less severe phenotypes and homozygotes develop rudimentary eyes and nasal processes and survive up to 36 hr after birth. Pax64Neu results in an amino acid substitution within the third helix of the homeodomain. Three-dimensional modeling indicates that the amino acid substitution interrupts the homeodomain recognition α-helix, which is critical for DNA binding. Whereas cooperative dimer binding of the mutant homeodomain to a paired-class DNA target sequence was eliminated, weak monomer binding was observed. Thus, a residual function of the mutated homeodomain may explain the hypomorphic nature of the Pax64Neu allele. Pax67Neu is a base pair substitution in the Kozak sequence and results in a reduced level of Pax6 translation product. The Pax64Neu and Pax67Neu alleles may be very useful for gene-dosage studies.