Mice doubly deficient in the midkine and pleiotrophin genes exhibit deficits in the expression of β-tectorin gene and in auditory response

Abstract

a-Tectorin and b-tectorin are major noncollagenous proteins of the tectorial membrane, which plays a crucial role in the reception of sonic signals in the cochlea. Midkine and pleiotrophin are closely related proteins that serve as growth factors and cytokines. In mice doubly deficient in the midkine gene and pleiotrophin gene, expression of b-tectorin mRNA was nearly abolished in the cochlea on day 1 and 7 after birth. Expression of atectorin mRNA was unaffected in the double knockout mice, and expression of b-tectorin mRNA was not altered in mice deficient in only the midkine or pleiotrophin gene. In newborn wild-type mice, both midkine and pleiotrophin were expressed in the greater epithelial ridge of the cochlea, in which b-tectorin mRNA was strongly expressed. These results indicate that either midkine or pleiotrophin is required for significant expression of b-tectorin. In agreement with the view that b-tectorin is essential for normal auditory function, mice doubly deficient in both midkine and pleiotrophin genes exhibited very severe auditory deficits. We observed that mice deficient in either midkine or pleiotrophin gene were also impaired in their auditory response, but the level of the deficit was generally low or moderate. The present finding illustrates the importance of growth factor expression in the cochlea for auditory function.

Increased trabecular bone formation in mice lacking the growth factor midkine

“…Moreover, since the rather subtle phenotypes caused by the single-gene deletions suggested the existence of functional redundancies, mice lacking both genes were generated as well. (19,20) These mice were not born at the expected Mendelian ratio and further displayed a severe reduction in body size of yet unknown origin. Moreover, while female Mdk/Ptn-deficient mice were infertile, an impairment of the auditory response has been reported as an ORIGINAL ARTICLE J JBMR additional phenotype.…”

The Angiogenic Growth Factor and Biomarker Midkine Is a Tumor-Shared Antigen

“…Although required for neuronal embryogenesis, its role in adults rarely appears beneficial, as MDK seems to participate in ischemic renal injury (16) and autoimmune responses (17). Accordingly, MDK-deficient mice do not exhibit serious developmental abnormalities (16,31), and mice vaccinated with peptides and DNA in our studies did not show any signs of autoimmunity. Finally, its crucial role in tumor growth is expected to limit tumor escape from immune attack through its selective loss.…”

Functional Receptors and Intracellular Signal Pathways of Midkine (MK) and Pleiotrophin (PTN)

“…Mouse models with either MK or PTN genes knocked out exhibited similarly moderate abnormalities [4][5][6] while those with both MK and PTN simultaneously knocked out displayed severe abnormalities. [7][8][9][10] These results indicate that the functions of MK and PTN are overlapped. Indeed, MK and PTN both have similar functions that include mitogenicity, cellular survival, oncogenicity, inflammation, differentiation and stem cell renewal (Fig.…”