title: Accelerated mortality from hydrocephalus and pneumonia in mice with a combined deficiency of SPAG6 and SPAG16L reveals a functional interrelationship between the two central apparatus proteins.
abstract: SPAG6 and SPAG16L are proteins localized to the "9+2" axoneme central apparatus. Both are essential for sperm motility and male fertility. These two proteins are also expressed in other tissues containing ciliated cells, such as brain and lung. To study the effects of combined deficiency of these two proteins, a double mutant mouse model was created. The double mutant mice displayed a more profound phenotype of growth retardation and hydrocephalus compared to mice nullizygous for SPAG6 and SPAG16L alone. The double mutant mice died younger, and mortality was significantly higher than in single mutant mice. In addition, the double mutant mice demonstrated pneumonia and its complications, including hemorrhage, edema, and atelectasis, phenotypes not observed in mice nullizygous for mutations in the individual genes. No other cilia-related phenotypic change was detected in double mutant mice including lateralization defects. The ultrastructure of cilia in both the brain and lung of the double mutant mice appeared normal. This model of combined SPAG6 and SPAG16L deficiency provides a new platform to study primary ciliary dyskinesia. The findings also demonstrate that SPAG6 and SPAG16L have related roles in controlling the function of cilia in the brain and lung.
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University, Richmond, Virginia 23298, USA. zzhang4@vcu.edu
authors.forename: Zhibing
authors.initials: Z
authors.lastname: Zhang
authors.forename: Waixing
authors.initials: W
authors.lastname: Tang
authors.forename: Rong
authors.initials: R
authors.lastname: Zhou
authors.forename: Xuening
authors.initials: X
authors.lastname: Shen
authors.forename: Zhangyong
authors.initials: Z
authors.lastname: Wei
authors.forename: Aatish M
authors.initials: AM
authors.lastname: Patel
authors.forename: John T
authors.initials: JT
authors.lastname: Povlishock
authors.forename: Jean
authors.initials: J
authors.lastname: Bennett
authors.forename: Jerome F
authors.initials: JF
authors.lastname: Strauss
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000648:ultrastructure; D002923:Cilia / Q000235:genetics / Q000648:ultrastructure; D006579:Heterozygote; D006849:Hydrocephalus / Q000235:genetics / Q000401:mortality*; D008168:Lung / Q000000981:diagnostic imaging / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D008868:Microtubule Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D011014:Pneumonia / Q000235:genetics / Q000401:mortality*; D011859:Radiography
chemical_list: D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; C491467:PF20 protein, mouse; C504274:SPAG6 protein, mouse