BAR HARBOR -- Researchers at The Jackson Laboratory have found a chromosomal region that interacts with the tub mutation to prevent normally occurring deafness in the tubby mouse model. Identification of the protective gene could help define shared molecular pathways underlying the multiple defects in tubby, including maturity-onset obesity, insulin resistance, and blindness.
The region, or locus, is known as moth1 (modifier of tubby hearing 1) and was traced to mouse Chromosome 2 by Drs. Akihiro Ikeda and Qing Yin Zheng in the laboratory of Drs. Patsy M. Nishina and Jrgen K. Naggert with colleagues from The Jackson Laboratory. The research appears as the cover article in the September 1999 issue of the journal Human Molecular Genetics.
The tubby mouse was characterized at the Laboratory in 1990 by Drs. Douglas Coleman and Eva Eicher as an autosomal recessive mutation in C57BL/6J ("B6") mice, one of a growing number of single-gene obesity models that includes ob (obese), db (diabetes), and cpefat. Tub was cloned in 1996 by the Nishina/Naggert group at The Jackson Laboratory and identified as a novel gene on chromosome 7.
Dr. Nishina and her colleagues have found that the tub mutation is a member of a novel family of genes that is widely distributed among species, from humans to maize. They have characterized TUB, the human homolog of tub, and family members called Tubby-Like Proteins: TULP1, TULP2, and TULP3. These mutated genes cause sensory defects in mice similar to retinitis pigmentosa and cone-rod dystrophy in humans.
Tubby mice develop hearing problems at three weeks of age, experiencing
cochlear degeneration due to progressive loss of hair cells and neurons. Normal
hearing results when sound waves cause the tiny hairs to oscillate, with the
movement transmitted as electrical impulses through the hair cells to the brain.
Hearing ability in mice is measured with a technique known as auditory brainstem
Contact: Luther Young