Phenotypes for Mgat1 Tg(Stra8-icre)1Reb MGI:6888114 MGI Mouse

abnormal male germ cell morphology ( J:185823 )

• at 7 weeks of age, testis sections show essentially no binding of the plant lectins Phaseolus vulgaris leucoagglutinin (L-PHA) and Griffonia simplicifolia agglutinin (GSA) to male germ cells, indicating the absence of complex N-glycans on germ cell glycoproteins

• in contrast, male germ cells in all tubules show binding of concanavalin A (Con A), a lectin that binds preferentially to high-mannose N-glycans

multinucleated giant male germ cells ( J:185823 , J:260130 )

• at 7 weeks of age, all seminiferous tubules contain multinucleated giant cells (MNCs) or symplasts in the region normally occupied by spermatids; MNCs are composed of either round or elongating spermatids, suggesting that germ differentiation proceeds to some extent (J:185823)

• at 22 weeks of age, small MNCs are occasionally detected in the epididymides (J:185823)

• at 24 and 25 dpp, fusion of cells adjacent to the lumen is observed in a few tubules (J:260130)

• at 28 dpp, ~14% of tubules contain multinucleated cells composed of fused spermatids (J:260130)

increased male germ cell apoptosis ( J:185823 )

• at 7 weeks of age, the % of tubules containing apoptotic cells is ~90% versus ~25% in control males, as determined by a TUNEL assay; the total number of apoptotic cells per TUNEL+ tubule is increased by ~3.5-fold

• however, parenchymal cells outside the tubules appear unaffected

abnormal seminiferous tubule morphology ( J:185823 )

• at 7 weeks of age, seminiferous tubule architecture is severely disrupted, with all tubules containing multinucleated giant male germ cells

decreased testis weight ( J:185823 )

• at 7 weeks of age, testis weight is reduced by ~33% relative to that in control males

• testis-to-body weight ratio is significantly decreased at both 7 and 22 weeks of age

abnormal testis physiology ( J:185823 )

• decapsulated testis extracts are completely sensitive to endoglycosidase H (Endo H), an enzyme that cleaves only high-mannose and hybrid N-glycans, but not complex N-glycans, indicating that male germ cells produce no detectable complex N-glycans

abnormal spermatogenesis ( J:185823 )

azoospermia ( J:185823 , J:260130 )

• 7-week-old males are unable to produce sperm; epididymides are completely devoid of spermatozoa at 22 weeks of age (J:185823)

• at 28 dpp, no mature spermatozoa are present in testis sections (J:260130)

decreased elongated spermatid number ( J:260130 )

• at 25 dpp, few elongated spermatids are observed

arrest of spermatogenesis ( J:260130 )

• starting at 24 and 25 dpp, fusion of cells adjacent to the lumen is observed in a few tubules

• at 28 dpp, number of tubules with elongated spermatids is significantly decreased and multinucleated germ cells, but no mature spermatozoa, are present

• premature upregulation of genes normally expressed later in spermatogenesis and spermiogenesis is observed at 22 and 23 dpp

• EGFR and PDGFRA transcripts and ERK1/2 signaling are decreased in 22 dpp male germ cells

• however, the number of Sertoli cells, spermatogonia, spermatocytes and stage VI and beyond tubules are relatively normal at 24-26 dpp

abnormal epididymis morphology ( J:185823 )

• at 22 weeks of age, epididymides are completely devoid of spermatozoa but occasionally contain small multinucleated giant cells (MNCs) or aberrant spermatids

• degenerate germ cells accumulate in the epididymides of adult males

male infertility ( J:185823 , J:260130 )

• all males fail to generate progeny after mating with two or more wild-type females (J:185823)

(J:260130)

decreased body weight ( J:185823 )

• at 22 weeks of age, male body weight is significantly lower than in control males

• however, male body weight is normal at 7 weeks of age