We have identified and cloned a point mutation in the mouse homolog of the unc-79 gene, to which the allele name Lightweight was assigned due to the resultant phenotypic traits. The Lightweight mutation creates a premature stop codon in the middle of the unc-79 protein. We introgressed a ∼1.4 Mb region surrounding the Lightweight mutation fully onto the C57BL/6J genetic background. Lwt/Lwt homozogotes are born at the expected Mendelian ratios and appear normal at birth, but survive a maximum of two days, similar to what has been reported for a knockout allele of this gene [29]. Although Lightweight heterozygotes exhibit a normal birthweight, soon thereafter and as adults, body weight is significantly less than their wild-type littermates. In addition, Lightweight heterozygotes have increased lean tissue and reduced body fat in comparison to wild-type littermates. Furthermore, Lightweight heterozygotes consume more food on a B6 background and more water on a B6D2 F1 background. Together, these results suggest a higher metabolic rate, increased protein turnover, or differences in energy usage.
