Abolition of lemniscal barrellette patterning in Prrxl1 knockout mice: Effects upon ingestive behavior

Abstract

Ingestive behaviors in mice are dependent on orosensory cues transmitted via the trigeminal nerve, as confirmed by transection studies. However, these studies cannot differentiate between deficits caused by the loss of the lemniscal pathway vs. the parallel paralemniscal pathway. The paired-like homeodomain protein Prrxl1 is expressed widely in the brain and spinal cord, including the trigeminal system. A knockout of Prrxl1 abolishes somatotopic barrellette patterning in the lemniscal brainstem nucleus, but not in the parallel paralemniscal nucleus. Null animals are significantly smaller than littermates by postnatal day 5, but reach developmental landmarks at appropriate times, and survive to adulthood on liquid diet. A careful analysis of infant and adult ingestive behavior reveals subtle impairments in suckling, increases in time spent feeding and the duration of feeding bouts, feeding during inappropriate times of the day, and difficulties in the mechanics of feeding. During liquid diet feeding, null mice display abnormal behaviors including extensive use of the paws to move food into the mouth, submerging the snout in the diet, changes in licking, and also have difficulty consuming solid chow pellets. We suggest that our Prrxl1(-/-) animal is a valuable model system for examining the genetic assembly and functional role of trigeminal lemniscal circuits in the normal control of eating in mammals and for understanding feeding abnormalities in humans resulting from the abnormal development of these circuits.

Impaired trigeminal control of ingestive behavior in the Prrxl1- / - mouse is associated with a lemniscal-biased orosensory deafferentation

“…Deafferentation studies (e.g., (5), reviewed in ( 13)) have clearly identified trigeminal afference as a key source of the peripheral feedback signals driving ingestive behavior in rodents. The data in the present study were obtained in a preparation quite different from deafferented rats, and also quite different from the Prrxl1 -/-KO described in (8). In neither of these earlier studies could the animals generate the ingestive behaviors required to maintain themselves on hard food.…”

“…One possible explanation is that KO mice may exhibit inefficient eating behavior, such that when they bite the hard food pellets, a portion is lost on the cage floor as small fragments that could not be measured in the present experiment. An inefficient "sloppy eater" phenotype was previously observed in Prrxl1 -/animals that were reared and maintained on a liquid diet (8). We next sought to quantify their eating efficiency for sweet hard food (sugared cereal), which is strongly preferred by the mice.…”

“…Range of ages, in months, for both groups was similar (WT 2.3-7.6 starting, 13.6-22.6 ending; KO 4.6-7.6 starting, 12.9-21.1 ending). The Prrxl1 -/mice, also known as the DRG11 line in the literature (6,7), were generated in the Feinstein lab at Hunter College (8).…”

“…The Prrxl1 -/animal exhibits many of the deficits seen in the (recovered) peripherally deafferented rat. These include reduced eating efficiency, a reduced body weight, difficulty consuming hard food, and marked incisor overgrowth (8)(9)(10), reflecting the absence of the normal pattern of bruxism seen in rats with intact orosensory input from the incisors (11). The present study was designed to examine the ingestive behavior of this mutant at both a high temporal resolution and over extended timespans, so as to obtain baseline behavioral measures for future studies.…”

Impaired trigeminal control of ingestive behavior in the Prrxl1-/- mouse is associated with a lemniscal-biased orosensory deafferentation

“…The Prrxl1 - /— animal exhibits many of the deficits seen in the (recovered) peripherally deafferented rat. These include reduced eating efficiency, a reduced body weight, difficulty consuming hard food, and marked incisor overgrowth [ 9 – 11 ], reflecting the absence of the normal pattern of bruxism seen in rats with intact orosensory input from the incisors [ 12 ]. The present study was designed to examine the ingestive behavior of this mutant at both a high temporal resolution and over extended timespans, so as to obtain baseline behavioral measures for future studies.…”