Mice homozygous for the "big giant head" mutation (bgh/bgh; Spef2bgh/bgh) have several abnormalities commonly associated with primary ciliary dyskinesia (PCD); including hydrocephalus, sinusitis and male infertility. Homozygous mice do not exhibit situs inversus. Heterozygous mice are viable and fertile with no abnormal phenotype. The absence of full-length protein was confirmed by western blot analysis on testis extracts from homozygotes.
The donating investigator has assessed homozygous phenotype on three different backgrounds: C57BL/6J-congenic (B6J.bgh/bgh), 129S6/SvEvTac-congenic (129S6.bgh/bgh) and an F1 cross of these two backgrounds ((B6x129)F1.bgh/bgh). Overall, the severity of morphological brain damage is background strain-dependent. Alterations in astrocytosis, microglial activation, myelination, and the neuronal population were identified and are generally more severe on the C57BL/6J background. Specific details follow.
B6J.bgh/bgh mice exhibit lethal hydrocephalus (average death ~ 1 month of age) with damage to multiple cell types, as well as cilia-driven cerebrospinal fluid flow deficit, sinusitis and male infertility. B6J.bgh/bgh also exhibit upper airway abnormalities (reduced respiratory ciliary motility, but no ultrastructural defects); although no major cellular, developmental or inflammatory abnormalities in the lower airway are reported. The donating investigator reports that B6J.bgh/bgh mice do not exhibit situs inversus. Heterozygous mice (B6J.bgh/+) are viable and fertile with no abnormal phenotype.
129S6.bgh/bgh mice do not develop gross hydrocephalus or exhibit early mortality, although they have cilia-driven cerebrospinal fluid flow deficits and variable levels of ventricular enlargement and brain damage. The sinusitis phenotype and male fertility phenotype for 129S6.bgh/bgh mice has not been characterized to date (although the donating investigator expects it to be similar to B6J.bgh/bgh animals). The specific upper airway vs. lower airway phenotype described for B6J.bgh/bgh has not been tested in 129S6.bgh/bgh to date (July 2015). The donating investigator reports that 129S6.bgh/bgh mice do not exhibit situs inversus. Heterozygous mice (129S6.bgh/+) are viable and fertile with no abnormal phenotype.
(B6x129)F1.bgh/bgh mice exhibit sinusitis and male infertility, but no evidence of gross hydrocephalus or early mortality. (B6x129)F1.bgh/bgh also exhibit upper airway abnormalities (reduced respiratory ciliary motility, but no ultrastructural defects); although no major cellular, developmental or inflammatory abnormalities in the lower airway are reported. The infertility in (B6x129)F1.bgh/bgh males results from reduction in the number of elongating spermatids during spermiogenesis and structural defects in sperm flagella (this could not be tested directly in B6J.bgh/bgh males because they die before sexual maturity). The donating investigator reports that (B6x129)F1.bgh/bgh mice do not exhibit situs inversus. Heterozygous mice ((B6x129)F1.bgh/+) are viable and fertile with no abnormal phenotype. Compared to similarly treated (B6x129)F1 wildtype mice, the (B6x129)F1.bgh/bgh mice show increased lymphocytic response when challenged with Streptococcus pneumonia infection.
