Phenotypes for Tg(Dyrk1a)189N3Yah MGI:5430593 MGI Mouse

lethality, incomplete penetrance ( J:182294 )

• viability is about 38% compared to the expected 50%

shortened head ( J:182294 )

• reduction in body weight during entire preweaning period continuing into adulthood, with a 20% reduction in weight at P30, however by P60, weight is normal

decreased body length ( J:182294 )

• reduction in body length during entire preweaning period continuing into adulthood, with a 20% reduction in length at P30, however by P60, length is normal

postnatal growth retardation ( J:182294 )

• developmental delay is seen at P15 and P30, however by P60, no difference is observed

shortened head ( J:182294 )

increased brain size ( J:182294 )

• the dorso-ventral length of the brain is enlarged

• increase in height of the central and more caudal part of the brain

increased brain weight ( J:182294 )

• brain weight is larger at P21 but not at P0, averaging a 15% increase by adulthood

abnormal lateral ventricle morphology ( J:182294 )

• increase in lateral ventricle volume

abnormal third ventricle morphology ( J:182294 )

• increase in dorsal third ventricle volume, however the ventral third ventricle is unchanged

abnormal thalamus morphology ( J:182294 )

• increase in ventral posterolateral and ventral posteromedial thalamic nuclei volume (120% of control)

• 18% increase in cell density in the ventral posterolateral and ventral posteromedial thalamic nuclei due to higher neuronal density. however glial density is unchanged

abnormal hippocampus morphology ( J:182294 )

• increase in hippocampal CA1-CA3 volume (115% of control)

abnormal dentate gyrus morphology ( J:182294 )

• increase in dentate gyrus volume (115% of control)

abnormal hippocampus molecular cell layer ( J:182294 )

• increase in hippocampal molecular layer volume but a decrease in cell density, indicating that total cell number is unchanged and that cell morphology is altered

abnormal hippocampus stratum oriens morphology ( J:182294 )

• increase in hippocampal oriens layer volume but a decrease in cell density, indicating that total cell number is unchanged and that cell morphology is altered

abnormal somatosensory cortex morphology ( J:182294 )

• increase in cortical layer thickness at the somatosensory cortex; increase in thickness of cortical layers II/III, V, and VI, but no difference in layer IV

• 15% increase in thickness of cortical layers V and VI

• 13% increase in total thickness of the entorhinal cortex

• density of NeuN-labeled neurons in layers V and VI of the somatosensory cortex is decreased by 15-17%, however density in layer II/III and IV is normal

• while there is an increase in thickness of layers V and VI of the somatosensory cortex, the density of neurons in these layers is decreased, indicating that the total number of neurons is unchanged

oligozoospermia ( J:324151 )

• at 3 months of age, total epididymal sperm count (relative to the weight of the epididymis) is significantly lower than in wild-type controls

abnormal spermatogonia morphology ( J:324151 )

• during the early stages of spermatogenesis, numbers of GFRalpha1+ undifferentiated spermatogonia A/spermatogonial stem cells (SCCs) are abnormally high, whereas numbers of differentiating spermatogonia A are normal

• number of STRA8+ spermatogonia B cells per seminiferous tubule is significantly higher than in wild-type controls

• SYCP3 (part of the synaptonemal complex normally found in early stages of meiosis I in primary spermatocytes) is aberrantly expressed in spermatogonia, with low SYCP3 expression in the cortical part of tubules (where spermatocytes are located) and strong SYCP3 expression close to the basal membrane (where spermatogonia are located)

abnormal seminiferous tubule morphology ( J:324151 )

• although STRA8 is normally located in the basal membrane, the number of STRA8+ seminiferous tubules is significantly higher than in wild-type controls

• however, the number, size, structure and cellular composition of seminiferous tubules is normal

decreased testis weight ( J:324151 )

• at 3 months of age, testis weight is significantly lower than in wild-type controls (both as a proportion of body weight or in absolute weight)

• however, testis histology is normal with no alterations in Leydig cell compartments

arrest of spermatogenesis ( J:324151 )

• males exhibit spermatogenesis failure in early stages of meiosis with excess numbers of spermatogonial stem cells

reduced male fertility ( J:324151 )

• 3-month-old male mice show a subtle or subclinical impairment in fertility, likely due to both central and peripheral defects, but can still produce offspring

abnormal enzyme/coenzyme level ( J:324151 )

• testis mRNA levels of the steroidogenesis enzymes Star (steroidogenic acute regulatory protein), Cyp11a1 (aka p450scc) and 3-beta-hydroxysteroid dehydrogenase (3betaHSD) are significantly lower than in wild-type controls, indicating defects in testis steroidogenesis

• in contrast, the level of Cyp17a1 (aka p450c17) mRNA is normal

abnormal hormone level ( J:324151 )

• testis levels of anti-Mullerian hormone (AMH) are significantly higher than in wild-type controls

abnormal circulating androgen level ( J:324151 )

• serum testosterone and delta-4 androstenedione levels are significantly lower than in wild-type controls, as measured by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS)

• however, serum progesterone, aldosterone, deoxycorticosterone and corticosterone levels are normal

decreased circulating testosterone level ( J:324151 )

• plasma testosterone levels are significantly lower than in wild-type controls, as measured by ELISA

• serum testosterone levels are significantly reduced, as determined by LC-MS/MS

decreased circulating gonadotropin level ( J:324151 )

• plasma levels of gonadotropic hormones, including plasma testosterone/luteinizing hormone (LH) ratio, are significantly lower than in wild-type controls, consistent with hypogonadotropic hypogonadism

decreased circulating follicle stimulating hormone level ( J:324151 )

• plasma FSH levels are significantly lower than in wild-type controls

decreased circulating luteinizing hormone level ( J:324151 )

• plasma LH levels are significantly lower than in wild-type controls